Copper(I) iodide catalyzed domino Knoevenagel hetero-Diels-Alder reaction of terminal acetylenes: Synthesis of pyrano[2,3-c]pyrazoles

Article abstract of DOI:10.1055/s-0028-1087380

A new and efficient CuI-catalyzed domino Knoevenagel hetero-Diels-Alder reaction of 1-oxa-1,3-butadienes with terminal unactivated acetylenes as building blocks to afford pyrano[2,3-c]pyrazoles has been developed. The products were obtained in good to hig

Full text of DOI:10.1055/s-0028-1087380

LETTER
55
Copper(I) Iodide Catalyzed Domino Knoevenagel Hetero-Diels–Alder
Reaction of Terminal Acetylenes: Synthesis of Pyrano[2,3-c]pyrazoles
S
ynthesis of Pyrano[2,
a
3-
c
]pyrazol
l
e
s
ihe Javan Khoshkholgh,a Saeed Balalaie,*a Hamid Reza Bijanzadeh,b Jürgen H. Grossc
a
Department of Chemistry, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran
Fax +98(21)22853650; E-mail: balalaie@kntu.ac.ir; E-mail: balalaie@yahoo.com
b
c
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Organisch-Chemisches Institut, Universitaet Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Received 25 September 2008
we present our investigation on the CuI-catalyzed domino
Knoevenagel–hetero-Diels–Alder reaction of pyrazolone
with terminal acetylenes as dienophile (Scheme1).
Abstract: A new and efficient CuI-catalyzed domino Knoevenagel
hetero-Diels–Alder reaction of 1-oxa-1,3-butadienes with terminal
unactivated acetylenes as building blocks to afford pyrano[2,3-
c]pyrazoles has been developed. The products were obtained in
good to high yields in most cases. Synthesis of polycyclic com-
pounds in one-pot, with easy workup, and mild reaction conditions
are advantages of our reported method.
R2
R1
O
OHC
O
R2
Key words: domino Reaction, hetero-Diels–Alder reaction, Knoe-
venagel condensation, cuprous iodide, alkynes, pyran
+
N
O
N
N
N
O
R1
Ar
Ar
The transition-metal-catalyzed alkyne cyclization has be-
come an important strategy for the synthesis of a wide va-
riety of heterocyclic structures.1,2 In recent years, efficient
copper-catalyzed reactions of alkynes have been devel-
oped.3 Copper(I) iodide is an inexpensive, nontoxic cata-
lyst, insensitive to air in comparison to other transition-
metal catalysts such as Pd, Pt, and Au. Therefore, CuI-
catalyzed cyclization has been accepted as a convenient
tool for the preparation of heterocycles.4
1
2
3
Scheme 1
Initially, we began our studies with the O-propargylated
salicylaldehydes 2a–g which are easily available via the
Williamson ether synthesis. To achieve and to optimize
the desired process, the reaction of compound 2a with 1a
was used as the model system to optimize the reaction
conditions. The experimental results are summarized in
Table 1.
In the development of new and efficient methodologies
for the synthesis of heterocyclic compounds, the domino
reaction has proved to be widely useful. Among these re-
actions, the domino Knoevenagel–hetero-Diels–Alder re-
action is a powerful tool for the construction of fused
heterocycles especially for the synthesis of pyran moi-
eties.5 This reaction is particularly suitable for alkenes;
however, the related process using alkynes has been far
less studied, due to the lower reactivity of unactivated
alkynes toward oxa-Diels–Alder reactions. Recently, we
reported a new example of CuI-catalyzed hetero-Diels–
Alder reaction of O-propargylated salicylaldehydes with
derivatives of barbituric acid.6 In order to enlarge the
scope of CuI-catalyzed [1,4] cycloaddition, we focused
our investigation on the domino intramolecular Knoeve-
nagel–hetero-Diels–Alder reaction with unactivated ter-
minal acetylenes.
Table 1 Domino Hetero-Diels–Alder Reaction of Aldehyde 2a with
1b in the Presence of Catalyst to Afford 3a
Entry
Lewis acid
(mol%)
Solvent
Base
Time
(h)a
Yield
(%)
1
2
3
4
5
6
7
–
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeCN
Et3N
–
20
20
12
8
–
CuI (20)
CuI (10)
CuI (20)
CuI (30)
CuI (40)
CuI (20)
–
Et3N
Et3N
Et3N
Et3N
Et3N
30
80
55
51
trace
8
8
20
Due to the importance of the pyrazole motif in drugs and
medicinal chemistry,7 we used the condensation product
of 2,4-dihydro-3H-pyrazol-3-ones with aldehydes as
heteroanalogues of 1,3-dicarbonyl compounds. Herein,
a Completion of the reaction.
The reaction of 1a with 2a and Et3N as base in methanol
under reflux in the absence of the catalyst did not provide
any of the desired product (entry 1). When CuI was em-
ployed as a catalyst, the desired product 3a was obtained
(entry 3). When the reaction was carried out without base,
no product was formed (entry 2). By variation of the ratio
SYNLETT 2009, No. 1, pp 0055–0058
x
x.
x
x.
2
0
0
8
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1087380; Art ID: D34008ST
© Georg Thieme Verlag Stuttgart · New York

56
M. J. Khoshkholgh et al.
LETTER
such as CuI is necessary to activate the triple bond further
by complexation. In analogy to the Cu(I)-catalyzed 1,3-
dipolar cycloaddition of azides and terminal alkynes9 and
Diels–Alder reaction of terminal acetylenes,10 theoretical
and experimental studies have been shown that a copper
acetylide must be generated for the reaction. Thus a simi-
lar postulated mechanism for the hetero-Diels–Alder can
be suggested (Scheme 2).
Table 2 CuI-Catalyzed Domino Hetero-Diels–Alder Reaction of
Aldehydes 2a–g with 1a,b
R2
R1
O
OHC
O
R2
CuI (20 mol%)
+
N
Et3N, methanol
reflux
O
N
N
N
O
R1
Ar
Ar
1a,b
2a–g
2a R1 = R2 = H
2b R1 = H, R2 = Br2
3a–j
R2
R1
O
1a Ar = 3-ClC6H4
1b Ar = Ph
2c R1 = H, R2 = NO2
2d R1 = H, R2 = Me
2e R1 = Br, R2 = Cl
2f R1 = Cl, R2 = Cl
2g R1 = OMe, R2 = H
R2
CHO
O
Et3N
CuI
+
N
N
O
N
N
O
R1
Ar
Ar
Entry
R1
H
R2
Ar
Yield (%)a,b
1
2
H
3-ClC6H4
Ph
80
82
78
85
89
81
85
78
80
85
H
Br
O
O
O
3
H
Br
3-ClC6H4
Ph
N
N
N
N
N
4
H
NO2
NO2
Me
Br
O
N
Ar
O
Cu
O
Cu
Cu
Ar
Ar
5
H
3-ClC6H4
3-ClC6H4
3-ClC6H4
Ph
6
H
7
Cl
Cl
Cl
OMe
O
8
Br
N
9
Cl
Ph
N
O
Ar
10
H
Ph
Scheme 2 Plausible mechanism for the domino Knoevenagel–
hetero-Diels–Alder reaction of terminal acetylene using CuI catalyst
a Reaction was carried out in MeOH at reflux conditions for 8 h in the
presence of 20 mol% CuI.
b Isolated yield.
Initial investigations have shown that some of the synthe-
sized pyrano[2,3-c]pyrazoles have interesting biological
properties such as anti-inflammatory, phosphatase inhibi-
tor, and cyclooxygenase 1 inhibitor. Further investiga-
tions for determination of various properties of these
compounds are in progress.
of CuI, we obtained a good yield with 20 mol% CuI. Us-
ing the optimized conditions, we prepared the pyrano[2,3-
c]pyrazoles 3a–j in 78–89% yield (Table 2).
The structures of the products were determined from spec-
troscopic data and high-resolution mass spectrometry.
Characteristic resonances for the compounds 3a–j in the
1H NMR spectra are an AB quartet for the OCH2 group
between d = 4.68 and 5.01 ppm followed closely by a sin-
glet for the OCH= group at d = 6.69–7.24 ppm. The cor-
responding signals of OCH2 and the shielded olefinic
carbon in the 13C NMR spectra appear at d = 63.4–68.6
and 83.7–96.4 ppm, respectively.
In conclusion, we have developed a new catalytic system
for the efficient domino hetero-Diels–Alder reaction of
unactivated terminal acetylene, which leads to the forma-
tion of the annulated pyrano[2,3-c]pyrazoles. Some of ad-
vantages of our work are synthesis of polycyclic
compounds in one-pot reaction, efficient C–C bond for-
mation, easy workup, mild reaction conditions, and high
yields. Investigations to find new domino hetero-Diels–
Alder reaction with unactivated terminal acetylene using
CuI catalyst and a detailed mechanistic study are under
way.
This reaction involves sequential Knoevenagel condensa-
tion between pyrazol-3-one 1a,b and the aldehydes 2a–g,
followed by the hetero-Diels–Alder reaction to afford
compounds 3a–j.8 The hetero-Diels–Alder reaction of 1-
oxa-1,3-butadienes with alkenes as a dienophile belongs
to the inverse electron-demand family in which the over-
lap of the LUMO of heterodiene with the HOMO of the
dienophile is most important. However, this interaction
Acknowledgment
We would like to acknowledge Prof. Rolf Gleiter for helpful discus-
sions. S.B. is grateful to the Iranian National Science Foundation
seems not to be sufficiently effective; therefore a catalyst (INSF) for the financial support.
Synlett 2009, No. 1, 55–58 © Thieme Stuttgart · New York

LETTER
Synthesis of Pyrano[2,3-c]pyrazoles
57
Light brown solid; mp 195–196 °C. IR (KBr): 1683, 1600
cm–1. 1H NMR (500 MHz, CDCl3): d = 2.49 (s, 3 H, Me),
4.70 (d, J = 12.0 Hz, 1 H, OCH), 4.71 (s, 1 H, CH), 4.83 (d,
J = 12.0 Hz, 1 H, OCH), 6.69 (s, 1 H, =CH), 6.72 (d, J = 8.6
Hz, 1 H, HAr), 7.18 (d, J = 2.2 Hz, 1 H, HAr), 7.24 (dd,
J = 8.6, 2.2 Hz, 1 H, HAr), 7.28 (t, J = 7.5 Hz, 1 H, HAr), 7.44
(t, J = 7.9 Hz, 1 H, HAr), 7.70 (d, J = 7.9 Hz, 2 H, HAr) ppm.
13C NMR (125 MHz, CDCl3): d = 13.5, 31.1, 67.2, 94.8,
109.7, 112.3, 118.4, 120.5, 125.9, 128.2, 128.5, 129.2,
134.9, 137.3, 145.7, 146.0, 152.3 ppm. HRMS (EI, 70 eV):
m/z calcd for C20H15N2O579Br [M]+: 394.0317; found:
394.0357; m/z calcd for C20H15N2O581Br [M + 2]+: 396.0297;
found: 396.0314.
References and Notes
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Int. Ed. 2003, 42, 3504. (b) Patil, N. T.; Wu, H.; Yamamoto,
Y. J. Org. Chem. 2005, 70, 4531. (c) Bertrand, P.; Gesson,
J. P. J. Org. Chem. 2007, 72, 3596.
(4) (a) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69,
5139. (b) Chen, C.; Dormer, P. G. J. Org. Chem. 2005, 70,
6964. (c) Zhu, W.; Ma, D. Chem. Commun. 2004, 888.
(d) Evindar, G.; Batey, R. J. Org. Chem. 2006, 71, 1802.
(e) Sreedhar, B.; Reddy, P. S.; Kumar, N. S. Tetrahedron
Lett. 2006, 47, 3055. (f) Jin, T.; Kamijo, S.; Yamamoto, Y.
Eur. J. Org. Chem. 2004, 3789.
(5) (a) Tietze, L. F.; Brasch, G.; Gericke, K. M. Domino
Reactions in Organic Synthesis; Wiley-VCH: Weinheim,
2006. (b) Tietze, L. F.; Rackelmann, N. Pure Appl. Chem.
2004, 76, 1967.
(6) Khoshkholgh, M. J.; Balalaie, S.; Gleiter, R.; Rominger, F.
Tetrahedron 2008, 64, 10924.
(7) (a) Elguero, J. In Comprehensive Heterocyclic Chemistry,
Vol. 5; Katritzky, A. P., Ed.; Pergamon Press: Oxford, 1984,
277–282. (b) Singh, S. K.; Reddy, P. G.; Rao, K. S.; Lohray,
B. B.; Misra, P.; Rajjak, S. A.; Rao, Y. K.; Venkatewarlu, A.
Bioorg. Med. Chem. Lett. 2004, 14, 499. (c) Chimenti, F.;
Bolasco, A.; Manna, F.; Secci, D.; Chimenti, P.; Befani, O.;
Turini, P.; Giovannini, V.; Mondovi, B.; Cirilli, R.; Torre,
F. L. J. Med. Chem. 2004, 47, 2017.
10-Bromo-3-(3-chlorophenyl)-1-methyl-3,11b-dihydro-
6H-chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3c)
White solid. IR (KBr): 1474 cm–1. 1H NMR (500 MHz,
DMSO-d6): d = 2.39 (s, 3 H, Me), 4.80 (s, 2 H, OCH2), 4.88
(s, 1 H, CH), 6.77 (d, J = 8.5 Hz, 1 H, HAr), 7.00 (s, 1 H,
=CH), 7.14 (s, 1 H, HAr), 7.29 (d, J = 8.5 Hz, 1 H, HAr), 7.36
(d, J = 7.9 Hz, 1 H, HAr), 7.49 (t, J = 7.9 Hz, 1 H, HAr), 7.67
(d, J = 7.9 Hz, 1 H, HAr), 7.73 (s, 1 H, HAr) ppm. 13C NMR
(125 MHz, DMSO-d6): d = 13.4, 30.1, 66.4, 95.4, 109.2,
110.9, 118.2, 118.7, 119.4, 125.6, 127.5, 129.3, 130.2,
130.6, 133.1, 135.7, 138.2, 145.5, 146.3, 152.3 ppm. HRMS
(EI, 70 eV): m/z calcd for C20H14N2O235Cl79Br [M]+:
427.9937; found: 427.9948; m/z calcd for
C20H14N2O235Cl81Br [M + 2]+: 429.9907; found: 429.9931;
m/z calcd for C20H14N2O237Cl81Br [M + 4]+: 431.9877;
found: 431.9912.
10-Nitro-1-methyl-3-phenyl-3,11b-dihydro-6H-
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3d)
Light brown solid; mp 208–209 °C. IR (KBr): 1678, 1601,
1514 cm–1; 1H NMR (500 MHz, CDCl3): d = 2.59 (s, 3 H,
Me), 4.80 (s, 1 H, CH), 4.83 (d, J = 12.1 Hz, 1 H, OCH), 4.93
(d, J = 12.1 Hz, 1 H, OCH), 6.78 (s, 1 H, =CH), 6.90 (d,
J = 8.9 Hz, 1 H, HAr), 7.29 (t, J = 7.7 Hz, 1 H, HAr), 7.44 (t,
J = 7.7 Hz, 2 H, HAr), 7.70 (d, J = 7.7 Hz, 2 H, HAr), 8.06 (dd,
J = 2.0, 8.9 Hz, 1 H, HAr), 8.09 (d, J = 2.0 Hz, 1 H, HAr) ppm.
13C NMR (125 MHz, CDCl3): d = 14.3, 31.8, 68.5, 108.6,
117.7, 121.1, 122.9, 124.3, 126.6, 127.7, 129.1, 136.5,
137.8, 159.2 ppm. HRMS (EI, 70 eV): m/z calcd for
C20H15N3O4 [M]+: 361.1063; found: 361.1066.
10-Nitro-3-(3-chlorophenyl)-1-methyl-3,11b-dihydro-
6H-chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3e)
Light brown solid; mp 215–216 °C. IR (KBr): 1686, 1599,
1580, 1510 cm–1. 1H NMR (500 MHz, DMSO-d6): d = 2.48
(s, 3 H, Me), 4.97 (s, 2 H, OCH and CH), 5.01 (s, 1 H, OCH),
7.00 (d, J = 9.0 Hz, 1 H, HAr), 7.24 (s, 1 H, =CH), 7.37 (dd,
J = 6.5, 1.0 Hz, 1 H, HAr), 7.51 (t, J = 8.0 Hz, 1 H, HAr), 7.67
(dd, J = 8.0, 1.0 Hz, 1 H, HAr), 7.74 (t, J = 2.0 Hz, 1 H, HAr),
7.87 (d, J = 1.8 Hz, 1 H, HAr), 8.05 (dd, J = 9.0, 2.8 Hz, 1 H,
HAr) ppm. 13C NMR (125 MHz, DMSO-d6): d = 13.9, 30.6,
66.3, 67.6, 95.5, 108.3, 117.8, 118.7, 119.9, 121.9, 124.1,
126.2, 127.7, 131.0, 133.6, 136.9, 138.5, 140.3, 145.9,
146.6, 159.2 ppm. HRMS (EI, 70 eV): m/z calcd for
C20H14N3O435Cl [M]+: 395.0673; found: 395.0663; m/z calcd
for C20H14N3O437Cl [M + 2]+: 397.0643; found: 397.0622.
3-(3-Chlorophenyl)-1,10-dimethyl-3,11b-dihydro-6H-
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3f)
(8) General Procedures for the Intramolecular Domino
Knoevenagel–Hetero-Diels–Alder Reaction
A solution of compounds 1a–g (1 mmol), 2a,b (1.2 mmol),
CuI (0.2 equiv, 38 mg), and Et3N (1 mmol, 0.06 mL) in
MeOH (25 mL) was refluxed for 8 h. The progress of
reaction was monitored by TLC. The precipitated solid was
filtered, washed with cold EtOH, and recrystallized in
CH2Cl2.
Selected Spectroscopic Data
3-(3-Chlorophenyl)-1-methyl-3,11b-dihydro-6H-
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3a)
White solid; mp 167–168 °C. IR (KBr): 1686, 1596 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.49 (s, 3 H, Me), 4.70 (d,
J = 12.0 Hz, 1 H, OCH), 4.71 (s, 1 H, CH), 4.86 (d, J = 12.0
Hz, 1 H, OCH), 6.69 (s, 1 H, =CH), 6.85 (d, J = 8.0 Hz, 1 H,
HAr), 6.91 (t, J = 7.3 Hz, 1 H, HAr), 7.07 (d, J = 7.6 Hz, 1 H,
HAr), 7.17 (t, J = 7.6 Hz, 1 H, HAr), 7.22 (d, J = 7.9 Hz, 1 H,
HAr), 7.33 (t, J = 8.0 Hz, 1 H, HAr), 7.64 (d, J = 8.1, 1 H,
HAr), 7.78 (s, 1 H, HAr) ppm. 13C NMR (125 MHz, CDCl3):
d = 8.4, 15.2, 62.7, 63.0, 83.9, 117.6, 118.9, 121.1, 121.7,
126.6, 129.3, 130.1, 130.7, 134.9, 153.2 ppm. HRMS (EI, 70
eV): m/z calcd for C20H15N2O535Cl [M]+: 350.0822; found:
350.0822; m/z calcd for C20H15N2O537Cl [M + 2]+: 352.0792;
found: 352.0783.
White solid; mp 194–195 °C. IR (KBr): 1683, 1597, 1512
cm–1. 1H NMR (500 MHz, CDCl3): d = 2.26 (s, 3 H, Me),
2.50 (s, 3 H, Me), 4.68 (d, J = 11.9 Hz, 1 H, OCH), 4.69 (s,
1 H, CH), 4.83 (d, J = 11.9 Hz, 1 H, OCH), 6.67 (s, 1 H,
=CH), 6.76 (d, J = 8.2 Hz, 1 H, HAr), 6.86 (s, 1 H, HAr), 6.97
(dd, J = 8.2, 1.7 Hz, 1 H, HAr), 7.23 (m, 1 H, HAr), 7.35 (t,
J = 8.0 Hz, 1 H, HAr), 7.65 (dd, J = 8.0, 1.7 Hz, 1 H, HAr),
7.79 (t, J = 2.0 Hz, 1 H, HAr) ppm. 13C NMR (125 MHz,
10-Bromo-1-methyl-3-phenyl-3,11b-dihydro-6H-
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3b)
Synlett 2009, No. 1, 55–58 © Thieme Stuttgart · New York

58
M. J. Khoshkholgh et al.
LETTER
8,10-Dichloro-1-methyl-3-phenyl-3,11b-dihydro-6H-
CDCl3): d = 14.2, 20.7, 31.5, 67.3, 96.4, 111.7, 117.0, 118.4,
120.6, 126.0, 126.1, 127.5, 128.7, 130.1, 130.2, 134.7,
134.8, 139.1, 146.5, 1147.4, 151.4 ppm. HRMS (EI, 70 eV):
m/z calcd for C21H17N2O235Cl [M]+: 364.0970; found
364.0959; m/z calcd for C21H17N2O237Cl [M + 2]+: 366.0949;
found 366.0964.
8-Bromo-10-chloro-3-(3-chlorophenyl)-1-methyl-3,11b-
dihydro-6H-chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole
(3g)
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3i)
White solid; mp 208–209 °C. IR (KBr): 1676, 1598, 1519
cm–1. 1H NMR (500 MHz, DMSO-d6): d = 2.39 (s, 3 H, Me),
4.91 (s, 1 H, CH), 4.92 (d, J = 12.0 Hz, 1 H, OCH), 4.96 (d,
J = 12.0 Hz, 1 H, OCH), 6.85 (d, J = 2.0 Hz, 1 H, HAr), 7.16
(s, 1 H, =CH), 7.31 (t, J = 7.5 Hz, 1 H, HAr),7.44 (d, J = 2.0
Hz, 1 H, HAr), 7.48 (t, J = 7.5 Hz, 2 H, HAr), 7.67 (d, J = 7.5
Hz, 2 H, HAr) ppm. 13C NMR (125 MHz, CDCl3): d = 13.7,
30.8, 67.8, 94.9, 108.6, 120.4, 121.6, 123.7, 124.0, 126.4,
127.6, 129.2, 130.7, 136.6, 137.3, 145.6, 145.8, 148.0 ppm.
HRMS (EI, 70 eV): m/z calcd for C20H14N2O235Cl2 [M]+:
384.0432; found: 384.0398; m/z calcd for
Light brown solid; mp 208.5–209.5 °C. IR (KBr): 1682,
1596 cm–1. 1H NMR (500 MHz, CDCl3): d = 2.46 (s, 3 H,
Me), 4.69 (s, 1 H, CH), 4.85 (d, J = 12.0 Hz, 1 H, OCH), 4.95
(d, J = 12.0 Hz, 1 H, OCH), 6.74 (s, 1 H, =CH), 6.96 (s, 1 H,
HAr), 7.23–7.42 (m, 3 H, HAr), 7.64 (d, J = 2.0 Hz, 1 H, HAr),
7.78 (d, J = 2.0 Hz, 1 H, HAr) ppm. 13C NMR (125 MHz,
CDCl3): d = 14.0, 31.7, 68.5, 95.2, 109.7, 111.5, 118.5,
120.7, 125.0, 125.8, 126.3, 130.1, 130.2, 131.2, 134.8,
135.6, 138.9, 146.3, 146.9, 149.1 ppm. HRMS (EI, 70 eV):
m/z calcd for C20H14N2O235Cl279Br [M]+: 461.9538; found:
461.9547; m/z calcd for C20H14N2O235Cl281Br [M + 2]+:
463.9517; found: 463.9500; m/z calcd for
C20H14N2O235Cl37Cl [M + 2]+: found: 386.0365; 386.0384;
m/z calcd for C20H14N2O237Cl2 [M + 4]+: 388.0373; found:
388.0368.
8-Methoxy-1-methyl-3-phenyl-3,11b-dihydro-6H-
chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3j)
Light brown solid; mp 214–215 °C. IR (KBr): 1686, 1597
cm–1. 1H NMR (500 MHz, CDCl3): d = 2.49 (s, 3 H, Me),
3.88 (s, 3 H, OMe), 4.75 (s, 1 H, CH), 4.83 (d, J = 12.0 Hz,
1 H, OCH2), 4.91 (d, J = 12.0 Hz, 1 H, OCH2), 6.68 (s, 1 H,
=CH), 6.74 (d, J = 7.7 Hz, 1 H, HAr), 6.80 (d, J = 7.7 Hz,
1 H, HAr), 6.87 (t, J = 7.9 Hz, 1 H, HAr), 7.26 (t, J = 7.3 Hz,
1 H, HAr), 7.42 (t, J = 7.8 Hz, 2 H, HAr), 7.70 (d, J = 7.9, 2 H,
HAr) ppm. 13C NMR (125 MHz, CDCl3): d = 12.0, 56.1,
63.4, 83.7, 115.1, 119.5, 121.1, 121.3, 121.5, 123.1, 126.6,
126.8, 127.7, 128.9, 129, 135.8, 141, 145.7, 147.4, 148.4
ppm. HRMS (EI, 70 eV): m/z calcd for C21H18N2O3 [M]+:
346.1318; found: 346.1331.
C20H14N2O235Cl37Cl81Br [M + 4]+: 465.9487; found:
465.9485.
8-Bromo-10-chloro-1-methyl-3-phenyl-3,11b-dihydro-
6H-chromeno[4¢,3¢:4,5]pyrano[2,3-c]pyrazole (3h)
White solid; mp 197.5–199 °C. IR (KBr): 1683, 1597, 1518
cm–1. 1H NMR (500 MHz, CDCl3): d = 2.47 (s, 3 H, Me),
4.68 (s, 1 H, CH), 4.84 (d, J = 12.0 Hz, 1 H, OCH), 4.95 (d,
J = 12.0 Hz, 1 H, OCH), 6.70 (s, 1 H, =CH), 6.99 (d, J = 2.1
Hz, 1 H, HAr), 7.28 (t, J = 7.7 Hz, 1 H, HAr),7.41 (d, J = 2.1
Hz, 1 H, HAr), 7.43 (t, J = 7.7 Hz, 2 H, HAr), 7.70 (d, J = 7.7
Hz, 2 H, HAr) ppm. 13C NMR (125 MHz, CDCl3): d = 14.1,
31.8, 68.6, 94.9, 109.4, 111.5, 120.9, 125.1, 125.8, 126.5,
129.1, 130.3, 131.1, 135.8, 137.8, 146.1, 146.3, 149.1 ppm.
HRMS (EI, 70 eV): m/z calcd for C20H14N2O235Cl79Br [M]+:
427.9928; found: 427.9980; m/z calcd for
(9) (a) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.;
Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem.
Soc. 2005, 127, 210. (b) Yoo, E. J.; Ahlquist, M.; Bae, I.;
Sharpless, K. B.; Fokin, V. V.; Chang, S. J. Org. Chem.
2008, 73, 5520.
(10) Fürstner, A.; Stimson, C. C. Angew. Chem. Int. Ed. 2007,
46, 8845.
C20H14N2O235Cl81Br [M + 2]+: 429.9907; found: 429.9946.
Synlett 2009, No. 1, 55–58 © Thieme Stuttgart · New York

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