Heck-mizoroki reaction OF 4-IODO-1H-pyrazoles

Article abstract of DOI:10.3987/COM-11-12146

The Heck-Mizoroki reaction of 1-protected-4-iodo-1H-pyrazoles with various kinds of alkenes was examined and found to yield 1-protected-4- alkenyl-1H-pyrazoles. P(OEt)3 was a suitable ligand for the cross-coupling reaction, together with the trityl group that acted as an appropriate protecting group of 1H-pyrazole.

Full text of DOI:10.3987/COM-11-12146

HETEROCYCLES, Vol. 83, No. 4, 2011
827
HETEROCYCLES, Vol. 83, No. 4, 2011, pp. 827 - 835. © The Japan Institute of Heterocyclic Chemistry
Received, 21st January, 2011, Accepted, 21st February, 2011, Published online, 2nd March, 2011
DOI: 10.3987/COM-11-12146
HECK-MIZOROKI REACTION OF 4-IODO-1H-PYRAZOLES
Yoshihide Usami,1ǂ* Hayato Ichikawa,1,2ǂ and Shinya Harusawa1
1Laboratory of Pharmaceutical Organic Chemistry, Osaka University of
Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan;
E-mail: usami@gly.oups.ac.jp
2Department of Applied Molecular Chemistry, College of Industrial Technology,
Nihon University, 1-2-1 Izumi-cho, Narashino, Chiba 275-8575, Japan (present
address)
ǂ Equal contribution
Abstract – The Heck-Mizoroki reaction of 1-protected-4-iodo-1H-pyrazoles
with various kinds of alkenes was examined and found to yield 1-protected-4-
alkenyl-1H-pyrazoles. P(OEt)3 was a suitable ligand for the cross-coupling
reaction, together with the trityl group that acted as an appropriate protecting
group of 1H-pyrazole.
INTRODUCTION
The exploration of new methods for the synthesis of heterocyclic compounds is an important work for
synthetic organic chemists, as most drugs or bioactive compounds possess one or more heterocyclic
moieties in their molecules. Pyrazoles are one of the most important classes of heterocyclic compounds1,2
and many pyrazole syntheses are based on the construction of a pyrazole ring by cycloaddition of
hydrazines with 1,3-dicarbonyl compounds or diazomethane with acetylenes in the last step. A novel
binuclear platinum(II) complex bearing 4-methylpyrazole (4mpz)3 as the ligand showed enhanced
antitumor activity in the cisplatin-resistant L1210/R cell line. The discovery of the 4mpz ligand
encouraged us to develop practical cross-coupling methods for the synthesis of novel C-4 substituted
pyrazoles. We have so far reported the synthesis of 4-arylpyrazoles by the Kumada coupling (Scheme 1,
eq. 1)4 or the Suzuki-Miyaura coupling (eq. 2),5 and the synthesis of 4-alkynylpyrazoles by the
Sonogashira coupling (eq. 3), which further provided 2H-indazoles by the double Sonogashira coupling
of bisiodo-1H-pyrazoles followed by the Bergman-Masamune cycloaromatization.6 As an extension of
our synthetic studies of 4-functionalized 1H-pyrazoles, we next addressed the Heck-Mizoroki reaction,
which is widely applied to the preparation of substituted alkenes by the cross-coupling reaction between

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HETEROCYCLES, Vol. 83, No. 4, 2011
alkenyl compounds and arylhalides or aryltriflates in the presence of palladium(0) catalysts.7-9 Ying and
co-workers reported the Heck-Mizoroki reaction between 4-bromo-1,3,5-trimethylpyrazole and tert-butyl
acrylate in the presence of IMes-Pd(dmba)Cl (4 mol %) in the development of a new Pd catalyst, but the
yield was only 32%.10 As far as we know, this is the only example of the Heck-Mizoroki reaction of 4-
halopyrazole.10-12 In this article, we describe the direct alkenylation of 4-iodo-1H-tritylpyrazole (1a) using
the Heck-Mizoroki reaction.
0.2 mol % Pd(OAc)2
4 mol % P(OEt)3
Tr
Tr
Tr
Tr
N
N
N
N
eq. 14
eq. 25
eq. 36
ArMgBr
ArB(OH)2
R
Br
Br
I
Ar
Ar
+
+
DMF/Et3N, 70 oC
5 mol % Pd(OAc)2
20 mol % PPh3, K2CO3
Tr
Tr
N
N
N
N
THF, reflux
1.0 mol % PdCl2(PPh3)2
5 mol % CuI
N
N
N
N
R
+
DMF/Et3N, rt
Scheme 1. Our previous work on the C-4 functionalization of 1H-tritylpyrazoles
RESULTS AND DISCUSSION
We first examined the Heck-Mizoroki reaction of 4-iodo-1H-tritylpyrazole (1a) with methyl acrylate in
the presence of Pd(OAc)2 (1 mol %), phosphine ligand, and triethylamine in DMF at 80 oC for 24 h. The
results are summarized in Table 1. In the absence of the phosphine ligand, 4-(2-methoxycarbonylvinyl)-1-
trityl-1H-pyrazole (2a) was obtained in only 46% yield (entry 1). 2a was assigned the E-configuration
from the coupling constant (15.9 Hz) between the double bond protons in the 1H-NMR spectrum. Use of
P(OEt)3 (4 mol %) as a ligand improved the yield of 2a to 95% (entry 4), whereas higher concentrations
of P(OEt)3 lowered the yield (entries 2 and 3). Reducing the amount of methyl acrylate from 5 to 1.2
equivalent in the presence of 4 mol % of P(OEt)3 afforded 2a in 95% yield (entry 5). Changing the ligand
from P(OEt)3 to PPh3 decreased the yield to 50% (entry 6), and increasing the amount of Pd(OAc)2 from 1
to 10 mol % had little effect on the yield (entry 7). From these results, we adopted the reaction conditions
of entry 5 as the general procedure for further studies.
To clarify the scope and limitations of the Heck-Mizoroki reaction of 1, the reactions of various 1-
protected 4-iodo1H-pyrazoles 1a-f with alkenes were carried out using the previous reaction conditions
(Table 1, entry 5), and the results are summarized in Table 2. From the results of entries 1-6 in Table 2,
the trityl group was confirmed to be a desirable N-1 protective group and benzyl groups were also an
acceptable protective group (entry 2). In the cases of p-toluenesulfonyl and 2,4,6-trimethylbenzoyl groups

HETEROCYCLES, Vol. 83, No. 4, 2011
829
Table 1. Heck-Mizoroki reaction of 1a
Pd(OAc)2 (1mol %)
ligand
Tr
N
Tr
N
N
I
CO2Me
+
DMF, Et3N
80 °C, 24 h
N
CO2Me
1a
2a
entry
methyl acrylate (eq.)
ligand (mol %)
---
2a (yield, %)
1
2
3
4
5
6
7
5
5
46
40
65
95
95
50
84a
P(OEt)3 (20)
P(OEt)3 (10)
P(OEt)3 (4)
P(OEt)3 (4)
PPh3 (4)
5
5
1.2
5
3
P(OEt)3 (15)
a) In entry 7, 10 mol % of Pd(OAc)2 was used.
(entries 3 and 4), the corresponding products (E)-2c and 2d were obtained in modest yields, whereas Boc-
and Cbz-substituted carbamates 1e and 1f were unfavorable as an N-1 protective group (entries 5 and 6).
We next focused on the reaction of 1a with various alkenes (entries 7-18). tert-Butyl acrylate and methyl
vinyl ketone were good coupling partners of 1a, affording 2g and 2h in 90% and 85% yields, respectively
(entries 7 and 8). Although most of the coupling reactions afforded selectively E-alkene products, the
reactions of 1a with methyl vinyl ketone (entry 8) or acrylonitrile (entry 13) gave a mixture of E- and Z-
isomers. The reactions of 1a with vinyl acetate (entry 10), acrolein (entry 11), diethyl vinylphosphonate
(entry 12), or acrylonitrile (entry 13) gave Heck products in low yields, accompanied by starting material
1a or dehalogenated 1-tritylpyrazole 3.
Although the reactions of 1a with some styrenes were examined (entries 14-17), the reactions gave (E)-
2n-q in low yields. Increasing the amounts of Pd(OAc)2 and P(OEt)3 in the reaction of 1a with styrene
improved somewhat the yield (entry 18). The results in Table 2 indicated the scope and limitations of our
procedure for the direct C-4 alkenylation of 1-protected -1H-pyrazoles via the Heck-Mizoroki reaction.
CONCLUSION
The synthesis of 1-protected-4-alkenyl-1H-pyrazoles from 1-protected-4-iodo-1H-pyrazoles using the
Heck-Mizoroki reaction was investigated. The results indicated that P(OEt)3, trityl group, and acrylates
were appropriate for use as a ligand, a protective group, and coupling partner in this reaction, respectively.
This study offered a new aspect in the direct functionalization of pyrazoles.

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HETEROCYCLES, Vol. 83, No. 4, 2011
Table 2. Heck-Mizoroki reactions between 1-protected-4-iodo-1H-pyrazoles 1 and various alkenes
Pd(OAc)2 (1 mol %)
P(OEt)3 (4 mol %)
R'
R
R
Tr
N
N
N
N
N
N
alkene
I
+
+
R'
DMF, Et3N
80 °C, 24 h
1a: R = Tr
1b: R = Bn
1c: R = Ts
1d: R = 2,4,6-trimethylbenzoyl
1e: R = Boc
(Z)-2h: R' = COMe
(Z)-2m: R' = CN
(E)-2a: R = Tr, R' = CO2Me
(E)-2b: R = Bn, R' = CO2Me
(E)-2c: R = Ts, R' = CO2Me
(E)-2d: R = 2,4,6-trimethylbenzoyl, R' = CO2Me
(E)-2e: R = H, R' = CO2Me
1f: R = Cbz
(E)-2f: R = Cbz, R' = CO2Me
(E)-2g: R = Tr, R' = CO2t-Bu
(E)-2h: R = Tr, R' = COMe
(E)-2i: R = Tr, R' = COmorphoryl
(E)-2j: R = Tr, R' = H
(E)-2k: R = Tr, R' = CHO
Tr
(E)-2l: R = Tr, R' = PO(OEt)2
(E)-2m: R = Tr, R' = CN
(E)-2n: R =Tr, R' = Ph
N
N
(E)-2o: R = Tr, R' = 4-F-Ph
(E)-2p: R = Tr, R' = 4-NO2-Ph
(E)-2q: R = Tr, R' = pyridin-2-yl
3
entry substrate
alkene
CH2=CHCO2Me
CH2=CHCO2Me
CH2=CHCO2Me
CH2=CHCO2Me
CH2=CHCO2Me
CH2=CHCO2Me
product (yield)
recovery of 1
recovery of 3
1a
1a
1b
1c
1d
1e
1f
(E)-2a (95%)
(E)-2b (75%)
(E)-2c (40%)
(E)-2d (56%)
(E)-2e (trace)
-
2
3
4
5
6
7
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
CH2=CHCO2tBu
methyl vinyl ketone
4-acryloylmorpholine
vinyl acetate
(E)-2g (90%)
(E)-2h (81%), (Z)-2h (4%)
(E)-2i (53%)
8
9
23%
47%
26%
47%
16%
69%
48%
34%
81%
10%
30%
10
11
12
13
14
15
16
17
18b
(E)-2j (6%)
CH2=CHCHO
(E)-2k (26%)
(E)-2l (8%)
CH2=CHPO(OEt)2
CH2=CHCN
21%
25%
20%
(E)-2m (28%), (Z)-2m (9%)
(E)-2n (9%)
CH2=CHPh (styrene)
4-fluorostyrene
p-nitrostyrene
(E)-2o (16%)
(E)-2p (5%)
4%
2-vinylpyridine
CH2=CHPh
(E)-2q (2%)
(E)-2n (44%)
a. The result is entry 5 in Table 1. b. 5 mol % of (PdOAc)2 and 10 mol % of P(OEt)3 were used in entry 18.

HETEROCYCLES, Vol. 83, No. 4, 2011
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EXPERIMENTAL
Unless otherwise indicated, all starting materials were obtained from commercial suppliers (Aldrich,
Kishida Chemical, Nacalai Tesque, Wako Pure Chemicals, and TCI) and used without further purification.
IR spectra were obtained with a JEOL FT/IR-680 Plus spectrometer. HRMS was determined with a JEOL
o
JMS-700 (2) mass spectrometer. NMR spectra were recorded at 27 C on Varian UNITY INOVA-500
and Mercury-300 spectrometers in CDCl3 with tetramethylsilane (TMS) as the internal standard. Melting
points were determined on a Yanagimoto micromelting point apparatus and are uncorrected. Liquid
column chromatography was conducted over silica gel (SiliCycle, SiliaFlash F60, 40-63 m). Analytical
TLC was performed on precoated Merck glass plates (silica gel 60 F254) and compounds were detected by
dipping the plates in an ethanol solution of phosphomolybdic acid, followed by heating.
Typical synthetic procedure (Table 1, entry 5): 4-Iodo-1H-tritylpyrazole (1a) (0.44 g, 1.0 mmol) and
Pd(OAc)2 (2.2 mg, 0.01 mmol) were dissolved in DMF (6 mL). The resulting solution was added
dropwise to a mixture of Et3N (1.2 mL), P(OEt)3 (6.9 µL, 0.04 mmol), and methyl acrylate (108 µL, 1.2
mmol). The reaction mixture was heated to 80 °C with stirring for 24 h under nitrogen atmosphere and
the resulting mixture was poured into water and extracted with CH2Cl2. The organic layer was washed
with brine, dried over MgSO4, filtered, and evaporated to furnish a crude product that was purified by
silica gel column chromatography (eluent: hexane/EtOAc = 4:1) to give 2a (0.36 g, 95%).
4-(2-Methoxycarbonylvinyl)-1-trityl-1H-pyrazole (2a): Colorless needles (CH2Cl2); mp 196199 °C;
1
IR (KBr) max 1699 (C=O), 1643 (C=C), 1493 (C=C) cm1; H-NMR (300 MHz, CDCl3): δ 7.87 (1H, s,
pyrazole-H), 7.55 (1H, s, pyrazole-H), 7.53 (1H, d, J = 15.9 Hz, -CH=CH-), 7.38–7.27 (9H, m, Tr-H),
13
7.20–7.12 (6H, m, Tr-H), 6.14 (1H, d, J = 15.9 Hz, -CH=CH-), 3.78 (3H, s, COOCH3); C-NMR (75
MHz, CDCl3): δ 167.6, 142.6, 138.8, 135.4, 132.8, 130.0, 128.0, 127.9, 116.9, 115.6, 79.1, 51.5; HRMS
m/z calcd for C26H22N2O2 (M+) 394.1682, found 394.1673.
1-Benzyl-4-(2-methoxycarbonylvinyl)-1H-pyrazole (2b): Colorless needles; mp 68 °C; IR (KBr) max
1707 (C=O), 1637 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.73 (1H, s, pyrazole-H), 7.54 (1H, d, J =
16.0 Hz, -CH=CH-), 7.536 (1H, s, pyrazole-H), 7.36–7.32 (2H, m Ph-H), 7.24–7.21 (2H, m, Ph-H), 6.15
13
(1H, d, J = 16.0 Hz, -CH=CH-), 5.28 (2H, s, NCH2Ph), 3.75 (3H, s, -COOCH3); C-NMR (75 MHz,
CDCl3): δ 167.6, 138.8, 135.6, 135.1, 129.5, 128.9, 128.3, 127.8, 118.6, 115.5, 56.2, 51.4; HRMS m/z
calcd for C14H14N2O2 (M+) 242.1055, found 242.1054.
4-(2-Methoxycarbonylvinyl)-1-tosyl-1H-pyrazole (2c): Colorless needles (CH2Cl2); mp 159160 °C;
1
IR (KBr) max 1716 (C=O), 1648 (C=C), 1588 (C=C) cm1; H-NMR (300 MHz, CDCl3): δ 8.22 (1H, s,
pyrazole-H), 7.91 (2H, d, J = 8.2 Hz, Ts-H), 7.87 (1H, s, pyrazole-H), 7.49 (1H, d, J = 16.1 Hz, -CH=CH-),

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HETEROCYCLES, Vol. 83, No. 4, 2011
7.34 (2H, d, J = 8.2 Hz, Ts-H), 6.24 (1H, d, J = 16.1 Hz, -CH=CH-), 3.76 (3H, s, -COOCH3), 2.42 (3H, s,
13
-PhCH3); C-NMR (75 MHz, CDCl3): δ 166.8, 146.4, 143.3, 133.3, 132.9, 130.4, 130.2, 128.3, 120.6,
119.3, 51.7, 21.7; HRMS m/z calcd for C14H14N2O4S (M+) 306.0674, found 306.0670.
4-(2-Methoxycarbonylvinyl)-1-(2,4,6-trimethylbenzoyl)-1H-pyrazole
(2d):
Colorless
crystals
(CH2Cl2); mp 134136 °C; IR (KBr) max 1725 (C=O), 1712 (C=O), 1645 (C=C), 1609 (C=C) cm1; 1H-
NMR (300 MHz, CDCl3): δ 8.50 (1H, br s, pyrazole-H), 7.89 (1H, s, pyrazole-H), 7.58 (1H, d, J = 16.1
Hz, -CH=CH-), 6.93 (2H, s, Ar-H), 6.33 (1H, d, J = 16.1 Hz, -CH=CH-), 3.80 (3H, s, COOCH3), 2.33
(3H, s, ArCH3), 2.15 (6H, s, 2x ArCH3); 13C-NMR (75 MHz, CDCl3): δ 166.9, 143.2, 140.2, 134.7, 133.1,
130.4, 128.2, 121.7, 119.6, 116.3, 56.2, 51.7, 21.2, 19.1; HRMS m/z calcd for C17H18N2O3 (M+) 298.1317,
found 298.1307.
4-(2-Methoxycarbonylvinyl)-1H-pyrazole (2e): Colorless needles (CH2Cl2); mp 9295 °C; IR (KBr)
1
max 1731 (C=O), 1649 (C=C) cm1; H-NMR (300 MHz, CDCl3): δ 9.00 (1H, br s, NH), 7.80 (2H, s,
pyrazole-H), 7.62 (1H, d, J = 15.9 Hz, -CH=CH-), 6.22 (1H, d, J = 15.9 Hz, -CH=CH-), 3.78 (3H, s,
13
COOCH3); C-NMR (75 MHz, CDCl3): δ 167.7, 135.2, 133.7, 117.9, 116.1, 51.6; HRMS m/z calcd for
C7H8N2O2 (M+) 152.0586, found 152.0582.
4-(2-tert-Butoxycarbonylvinyl)-1-trityl-1H-pyrazole (2g): Colorless crystals (CH2Cl2); mp
148152 °C; IR (KBr) max 1704 (C=O), 1638 (C=C), 1499 (C=C) cm1; 1H-NMR (300 MHz, CDCl3): δ
7.88 (1H, s, pyrazole-H), 7.57 (1H, s, pyrazole-H), 7.46 (1H, d, J = 15.9 Hz, -CH=CH-), 7.37–7.28 (9H,
13
m, Tr-H), 7.22–7.16 (6H, m, Tr-H), 6.13 (1H, d, J = 15.9 Hz, -CH=CH-), 1.53 (9H, s, -tBu); C-NMR
(75 MHz, CDCl3): δ 166.4, 142.6, 138.7, 133.9, 132.5, 130.0, 127.8, 127.1, 118.0, 117.0, 80.0, 79.0, 28.1;
HRMS m/z calcd for C29H28N2O2 (M+) 436.2151, found 436.2147.
4-[3-Oxo-(E)-1-butenyl]-1-trityl-1H-pyrazole [(E)-2h]: Colorless needles (CH2Cl2); mp 214216 °C;
1
IR (KBr) max 1667 (C=O), 1625 (C=C), 1541 (C=C) cm1; H-NMR (300 MHz, CDCl3): δ 7.89 (1H, s,
pyrazole-H), 7.59 (1H, s, pyrazole-H), 7.37 (1H, d, J = 16.8 Hz, -CH=CH-), 7.34–7.31 (9H, m, Tr-H),
13
7.25–7.13 (6H, m, Tr-H), 6.43 (1H, d, J = 16.8 Hz, -CH=CH-), 2.28 (3H, s, CH3); C-NMR (75 MHz,
CDCl3): δ 198.1, 142.4, 138.9, 134.1, 133.0, 130.0, 128.0, 127.9, 127.8, 125.6, 79.2, 27.0; HRMS m/z
calcd for C26H22N2O (M+) 378.1732, found 378.1734.
4-(3-Oxo-(Z)-1-butenyl)-1-trityl-1H-pyrazole ((Z)-2h): Colorless crystals (CH2Cl2); mp 163166 °C;
1
IR (KBr) max 1676 (C=O), 1580 (C=C), 1541 (C=C) cm1; H-NMR (300 MHz, CDCl3): δ 8.47 (1H, s,
pyrazole-H), 8.09 (1H, s, pyrazole-H), 7.40–7.27 (9H, m, Tr-H), 7.25–7.13 (6H, m, Tr-H), 6.55 (1H, d, J
= 8.2 Hz, -CH=CH-), 6.07 (1H, d, J = 8.2 Hz, -CH=CH-), 2.22 (3H, s, CH3); 13C-NMR (75 MHz,
CDCl3): δ 197.5, 143.4, 142.6, 136.3, 131.9, 130.0, 127.8, 121.4, 116.7, 79.0, 31.3 (lack of a carbon
signal probably because of overlap with one of the other aromatic carbon signals); HRMS m/z calcd for

HETEROCYCLES, Vol. 83, No. 4, 2011
833
C26H22N2O (M+) 378.1732, found 378.1724.
4-(2-Morphorylcarbonylvinyl)-1-trityl-1H-pyrazole (2i): White powder (CH2Cl2); mp 138141 °C; IR
(KBr) max 1649 (C=O), 1601 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.87 (1H, s, pyrazole-H), 7.55
(1H, d, J = 15.4 Hz, -CH=CH-), 7.54 (1H, s, pyrazole-H), 7.347.29 (9H, m, Tr-H), 7.187.12 (6H, m,
Tr-H), 6.56 (1H, d, J = 15.4 Hz, -CH=CH-), 3.68 (4H,br s), 3.676 (4H, br s); 13C-NMR (75 MHz, CDCl3):
δ 165.7, 142.6, 138.3, 133.7, 132.7, 130.0, 127.9, 127.8, 117.6, 114.2, 79.0, 66.8 (lack of a carbon signal
probably because of overlap with the carbon signal at 66.8 ppm); HRMS m/z calcd for C29H27N3O2 (M+)
449.2103, found 449.2100.
1-Trityl-4-vinyl-1H-pyrazole (2j): Colorless crystals (CH2Cl2); mp 127130 °C; IR (KBr) max 1641
(C=C), 1491 (C=C) cm1; 1H-NMR (300 MHz, CDCl3): δ 7.77 (1H, s, pyrazole-H), 7.36 (1H, s, pyrazole-
H), 7.34–7.30 (9H, m, Tr-H), 7.26–7.12 (6H, m, Tr-H), 6.46 (1H, dd, J = 17.7, 11.0 Hz, -CH=CHH), 5.43
(1H, d, J = 17.7 Hz, -CH=CHtransH), 5.04 (1H, d, J = 11.0 Hz, -CH=CHHcis); 13C-NMR (75 MHz,
CDCl3): δ 143.0, 137.3, 130.0, 127.9, 127.7, 126.8, 119.6, 111.9, 78.5 (lack of a carbon signal probably
because of overlap with one of the other aromatic carbon signals); HRMS m/z calcd for C24H20N2 (M+)
336.1626, found 336.1620.
4-(2-Formylvinyl)-1-trityl-1H-pyrazole (2k): Pale yellow powder (CH2Cl2); mp 211213 °C; IR (KBr)

max 1716 (C=O), 1676 (C=C), 1634 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 9.52 (1H, d, J = 7.9 Hz,
-CHO), 7.91 (1H, s, pyrazole-H), 7.64 (1H, s, pyrazole-H), 7.347.14 (16H, m, Tr-H, -CH=CHCHO),
6.42 (1H, dd, J = 15.7, 7.0 Hz, -CH=CHCHO); 13C-NMR (75 MHz, CDCl3): δ 193.4 (193.3), 143.4,
142.3, 139.3 (138.9), 133.4 (133.2), 130.0, 129.9, 127.9, 126.8, 116.9, 79.3; HRMS m/z calcd for
C25H20N2O (M+) 364.1576, found 364.1580.
4-{2-(P,P-Diethoxyphosphonyl)vinyl}-1-trityl-1H-pyrazole (2l): Colorless crystals (CH2Cl2); mp
1
97100 °C; IR (KBr) max 1621 (C=C) cm-1; H-NMR (300 MHz, CDCl3): δ 7.84 (1H, s, pyrazole-H),
7.52 (1H, s, pyrazole-H), 7.40–7.25 (9H, m, Tr-H), 7.18–7.11 (6H, m, Tr-H), 5.92 (1H, d, J = 18.0 Hz, -
CH=CH-), 5.87 (1H, d, J = 18.0 Hz, -CH=CH-), 4.10 (2H, q, J = 7.1 Hz, -PO(OCH2CH3)OEt), 4.07 (2H,
q, J = 7.1 Hz, -PO(OCH2CH3)OEt), 1.33 (6H, t, J = 7.1 Hz, -PO(OCH2CH3)2); 13C-NMR (75 MHz,
2
3
CDCl3): δ 142.5, 139.4 (d, JC-P = 6.9 Hz), 138.4, 132.5, 130.0, 127.8, 127.1, 117.8 (d, JC-P = 25.2 Hz),
1
2
3
110.1 (d, JC-P = 194 Hz), 79.1, 61.7 (d, JC-P = 4.6 Hz), 16.3 (d, JC-P = 5.7 Hz); HRMS m/z calcd for
C28H29N2O3P (M+) 472.1916, found 472.1918.
4-[(E)-2-Cyanovinyl]-1-trityl-1H-pyrazole ((E)-2m): Colorless needles (EtOAc-hexane); mp
1
233236 °C; IR (KBr) max 2214 (CN), 1629 (C=C), 1597 (C=C) cm-1; H-NMR (300 MHz, CDCl3): δ
7.84 (1H, s, pyrazole-H), 7.55 (1H, s, pyrazole-H), 7.387.28 (9H, m, Tr-H), 7.21 (1H, d, J = 16.6 Hz, -
CH=CH-), 7.187.10 (6H, m, Tr-H), 5.55 (1H, d, J = 16.6 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ

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HETEROCYCLES, Vol. 83, No. 4, 2011
142.3, 141.0, 138.0, 132.6, 130.0, 128.1, 127.9, 118.5, 116.6, 93.5, 79.3; HRMS m/z calcd for C25H19N3
(M+) 361.1579, found 361.1576.
4-[(Z)-2-Cyanovinyl]-1-trityl-1H-pyrazole [(Z)-2m]: colorless crystals (CH2Cl2); mp 182185 °C; IR
1
(KBr) max 2211 (CN), 1615 (C=C), 1492 (C=C) cm-1; H-NMR (300 MHz, CDCl3): δ 8.14 (1H, s,
pyrazole-H), 7.96 (1H, s, pyrazole-H), 7.387.28 (9H, m, Tr-H), 7.187.10 (6H, m, Tr-H), 6.96 (1H, d, J
= 11.7 Hz, -CH=CH-), 5.15 (1H, d, J = 11.7 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ 142.4, 140.1,
139.5, 133.5, 130.0, 127.9, 127.2, 118.2, 116.2, 91.6, 79.4; HRMS m/z calcd for C25H19N3 (M+) 361.1579,
found 361.1570.
4-(2-Phenylvinyl)-1-trityl-1H-pyrazole (2n): Colorless crystals (CH2Cl2); mp 225228 °C; IR (KBr)

max 1643 (C=C), 1490 (C=C) cm1; 1H-NMR (500 MHz, CDCl3): δ 7.86 (1H, s, pyrazole-H), 7.46 (1H, s,
pyrazole-H), 7.39 (2H, br d, J = 7.1 Hz, Ph-H), 7.35–7.25 (12H, m, Tr-H, Ph-H), 7.22–7.16 (6H, m, Tr-
13
H), 6.90 (1H, d, J = 16.5 Hz, -CH=CH-), 6.80 (1H, d, J = 16.5 Hz, -CH=CH-); C-NMR (125 MHz,
CDCl3): δ 143.5, 137.6, 130.4, 130.4, 130.1, 128.6, 127.9, 127.8, 127.6, 127.0, 125.8, 119.3, 118.7, 78.7;
HRMS m/z calcd for C30H24N2 (M+) 412.1939, found 412.1940.
4-[2-(4-Fluorophenyl)vinyl]-1-trityl-1H-pyrazole (2o): Colorless needles (CH2Cl2); mp 239242 °C; IR
(KBr) max 1641 (C=C), 1507 (C=C) cm1; 1H-NMR (500 MHz, CDCl3): δ 7.85 (1H, s, pyrazole-H), 7.45
(1H, s, pyrazole-H), 7.38–7.31 (11H, m, Tr-H, Ph-H), 7.22–7.15 (6H, m, Tr-H), 7.01 (1H, d, J = 8.7 Hz,
Ph-H), 6.97 (1H, d, J = 8.6 Hz, Ph-H), 6.83 (1H, d, J = 16.6 Hz, -CH=CH-), 6.73 (1H, d, J = 16.6 Hz, -
CH=CH-); 13C-NMR (125 MHz, CDCl3): δ 143.0, 137.5, 130.4, 130.1, 130.0, 127.9, 127.8, 127.4, 127.3,
119.2, 115.5 (d,2JC-F = 22.0 Hz), 78.7 (lack of a carbon signal probably because of overlap with one of the
other aromatic carbon signals); HRMS m/z calcd for C30H23FN2 (M+) 430.1845, found 430.1848.
4-[2-(4-Nitrophenyl)vinyl]-1-trityl-1H-pyrazole (2p): Yellow plates (CH2Cl2); mp 163168 °C; IR
(KBr) max 1637 (C=C), 1593 (C=C), 1509 (NO2), 1342 (NO2) cm1; 1H-NMR (300 MHz, CDCl3): δ 8.09
(2H, d, J = 8.8 Hz, -PhNO2), 7.83 (1H, s, pyrazole-H), 7.46 (1H, s, pyrazole-H), 7.41 (2H, d, J = 8.8 Hz,
-PhNO2), 7.28–7.04 (15H, m, Tr-H), 7.01 (1H, d, J = 16.6 Hz, -CH=CH-), 6.75 (1H, d, J = 16.6 Hz, -
13
CH=CH-); C-NMR (75 MHz, CDCl3): δ 142.8, 137.8, 131.4, 130.1, 129.0, 128.2, 127.9, 127.8, 126.1,
125.3, 124.5, 124.1, 118.6, 79.0; HRMS m/z calcd for C30H23N3O2 (M+) 457.1790, found 457.1786.
4-[1-(Pyridin-2-yl)vinyl]-1-trityl-1H-pyrazole (2q): White powder; mp 165168 °C; IR (KBr) max
1
1636 (C=C), 1585 (C=C) cm-1; H-NMR (300 MHz, CDCl3): δ 8.53 (1H, br d, J = 4.6 Hz, pyridinyl-H),
7.91 (1H, s, pyrazole-H), 7.69 (1H, m, pyridinyl-H), 7.55 (1H, s, pyrazole-H), 7.50 (1H, d, J = 16.1 Hz, -
13
CH=CH-), 7.38–7.10 (17H, m, Tr-H, pyridinyl-H), 6.88 (1H, d, J = 16.1 Hz, -CH=CH-); C-NMR (75
MHz, CDCl3): δ 143.1, 142.8, 142.0, 138.2, 136.2, 134.6, 131.8, 130.2, 130.1, 128.0, 127.75, 121.6,
121.5, 118.6, 78.9; HRMS m/z calcd for C29H23N3 (M+) 413.1982, found 413.1887.

HETEROCYCLES, Vol. 83, No. 4, 2011
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ACKNOWLEDGEMENTS
We are grateful to Ms. Mihoyo Fujitake of this University for MS measurement and Professor Masao
Arimoto, who retired from this University in 2009, for continuous encouragement. We thank Ms.
Megumi Ashino of Nihon University for experimental assistance during her internship program, as well
as Ms. Tomoko Matsushita and Mr. Yudai Suzuki of our laboratory. This work was supported in part by a
Grant-in-Aid for the “High-Tech Research Center” Project for Private Universities: matching fund
subsidy from MEXT (Ministry of Education, Culture, Sports, Science, and Technology), 20062009,
Japan and the Lonza Japan Award 2009 in Synthetic Organic Chemistry, Japan to H. I.
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