Silver(I)-catalyzed reaction between pyrazole and propargyl acetates: Stereoselective synthesis of the scorpionate ligands (E)-allyl-gem-dipyrazoles (ADPs)

Article abstract of DOI:10.1021/jo401867e

The reaction between readily accessible pyrazole and propargyl acetates in the presence of Ag(I) catalyst yielded a new class of (E)-allyl-gem-dipyrazole scorpionate ligands: 1-aryl-2-N-pyrazolyl allyl acetates and 1,3-dipyrazolyl-3-arylpropene. The reaction showed broad substrate scope, and various functional and protecting groups were tolerated under the reaction conditions. The palladium(II) scorpionate complex could thus be easily prepared and successfully employed in Suzuki-Miyaura cross-couplings in water.

Full text of DOI:10.1021/jo401867e

Article
pubs.acs.org/joc
Silver(I)-Catalyzed Reaction between Pyrazole and Propargyl
Acetates: Stereoselective Synthesis of the Scorpionate Ligands
(E)‑Allyl-gem-dipyrazoles (ADPs)
M. Bhanuchandra, Malleswara Rao Kuram, and Akhila K. Sahoo*
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
S
* Supporting Information
ABSTRACT: The reaction between readily accessible pyr-
azole and propargyl acetates in the presence of Ag(I) catalyst
yielded a new class of (E)-allyl-gem-dipyrazole scorpionate
ligands: 1-aryl-2-N-pyrazolyl allyl acetates and 1,3-dipyrazolyl-
3-arylpropene. The reaction showed broad substrate scope,
and various functional and protecting groups were tolerated
under the reaction conditions. The palladium(II) scorpionate
complex could thus be easily prepared and successfully
employed in Suzuki−Miyaura cross-couplings in water.
of pyrazole could afford (E)-1,1′-(3-arylprop-1-ene-1,3-diyl)-
bis(1H-pyrazole) (5).
INTRODUCTION
■
Propargyl alcohols readily undergo nucleophilic substitution
because of the presence of hydroxyl and alkyne functionalities
and hence can be used for the facile construction of complex
molecular frameworks.1 The reaction between 1-substituted
propargyl acetate and NH-heteroarenes allows for the
formation of (1) propargyl heteroarenes through substitution
of the hydroxyl group and its derivatives by the NH-
heteroarene, (2) 1,2-disubstituted allyl acetates via hydro-
amination of the NH moiety with the alkyne, (3) 1,3-
disubstituted allenes via attack of the heteroaryls at the
terminal position of the alkyne, and (4) allyl-gem-diheteroaryl-
and 1,3-diheteroaryl-substituted propenes through attack of the
NH heteroarene on the in situ generated allene. Thus, various
functionalized heteroarenes can be practically realized via a
single-step reaction between propargyl acetates and NH-
heteroarenes.2 Recently, Shi’s group demonstrated the synthesis
of propargyl and allene triazoles by the iron-catalyzed
regioselective attack of triazole on propargyl alcohols.2b,c The
Au-catalyzed synthesis of functionalized allenes from propargyl
alcohols and arenes has also been reported.1o Interestingly, gem-
dipyrazolylalkanes were easily synthesized from the Ag-
catalyzed regioselective attack of two pyrazoles at an aliphatic
terminal alkyne carbon center.2a Our recent work in the
development of novel reactions of propargyl alcohols inspired
us to explore the Lewis acid catalyzed reaction between
propargyl acetate and pyrazole.3 We anticipated the formation
of the rarely observed hydroamination compound 1-aryl-2-
pyrazolyl allyl acetate (3, path I), 1-aryl-3-pyrazolyl allene (A,
path II), and propargyl-N-pyrazole (6, path III) (Scheme 1).
Furthermore, α-attack of pyrazole on the transiently formed
allene pyrazole A could afford (E)-allyl-gem-dipyrazoles (4;
ADPs), a new class of scorpionate-type ligands, whereas γ-attack
Interestingly, the gem-dipyrazolyl derivatives exhibited
analgesic and anti-inflammatory activities.4 The two adjacent
nitrogen atoms in 4 give strong chelation ability to the metal,
and the complexes are useful in accomplishing various catalytic
organic transformations.5,6 Importantly, some of the Pt-
coordinated complexes show anticancer activity.7 We herein
report the synthesis of novel ADPs (4), 1-aryl-2-N-
pyrazolylallyl acetate (3), and 1,3-dipyrazolyl-3-arylpropene
(5) from propargyl acetates and pyrazoles in the presence of
AgNO3.
RESULTS AND DISCUSSION
■
To start with, 1-phenylprop-2-ynyl acetate (1a) and pyrazole
(2) were independently reacted in the presence of various
Lewis acids at 80 °C for 24 h. The details of the optimization
studies are shown in Table 1. The reaction between 1a (1.0
equiv) and 2 (5.0 equiv) with 10 mol % AgOTf in
chlorobenzene produced the (E)-allyl-gem-dipyrazole (ADP)
4a in 41% yield, 1-phenyl-2-N-pyrazolyl allyl acetate (3a; 18%),
and 1,3-dipyrazolyl-3-phenylpropene (5a; 20%) with incom-
plete consumption of 1a (entry 1). Gratifyingly, 4a, 3a, 5a, and
unreacted 1a were easily isolated through flash column
chromatography in pure form. Incomplete conversion of 1a
and poor overall yield of the products 3a−5a were noticed
when Cu(OTf)2, In(OTf)3, and CuNO3·H2O were independ-
ently employed (entries 2−4). The use of Ph3PAuCl or AuCl3
catalyst was not satisfactory, giving a complex reaction profile
with formation of a trace amount of 4a (entries 5 and 6).
Received: August 22, 2013
Published: November 4, 2013
© 2013 American Chemical Society
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Scheme 1. Reaction between Propargyl Acetate and Pyrazole
a
Table 1. Optimization of Reaction Conditions
b
yield (%)
entry
amt of 2 (equiv)
catalyst
AgOTf
solvent
3a
18
4a
5a
20
1
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.0
4.0
6.0
8.0
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
THF
41
<5
<6
<8
10
<5
58
<9
25
35
36
37
38
20
43
55
53
51
2
Cu(OTf)2
In(OTf)3
CuNO3·H2O
Ph3PAuCl
AuCl3
<1
<1
<2
n.d.
trace
21
<2
13
<2
<3
<7
n.d.
trace
11
<6
12
3
4
5
6
7
AgNO3
AgCl
8
9
Ag2CO3
AgBF4
10
11
12
13
14
15
16
17
18
17
18
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
18
16
CH3CN
10
29
DMF
22
17
DCE
08
12
chlorobenzene
chlorobenzene
chlorobenzene
chlorobenzene
25
08
21
10
20
18
21
19
a
b
Reactions were carried out using 1a (0.5 mmol) and catalyst (10 mol %) in solvent (0.5 mL) at 80 °C for 24 h. Isolated yields. n.d. = not detected.
To our delight, reaction with AgNO3 delivered an improved
of O-pivaloyl- or O-Boc-protected propargyl alcohols with
pyrazole produced poor amounts of the ADPs.8
yield of 4a (58%), though 3a and 5a were also isolated in 21%
and 11% yields, respectively (Table 1, entry 7). A trace amount
of products 3a−5a were noted in GC-MS, when the reaction
was conducted with AgCl (entry 8), whereas Ag2CO3 or AgBF4
had only a moderate influence (entries 9 and 10). Of the
various Ag salts examined, AgNO3 was found to be effective
(entry 7). It is worth mentioning that we did not observe even
a trace of propargyl-N-pyrazole 6.2b We next explored the effect
of solvents. Incomplete conversion of 1a with the formation of
a moderate amount of 4a was observed when polar aprotic
solvents such as THF, CH3CN, and DMF were used (entries
11−13). The reaction in DCE was poor (entry 14). The use of
different amounts of pyrazole was further investigated. The
loading of a lower amount of pyrazole, from 5.0 to 2.0 or 4.0
equiv, led to 4a with slightly decreased yield (entries 15 and
16). An enhanced yield of 5a was observed when 6.0/8.0 equiv
of 2 was employed (entries 17 and 18). We therefore used 5.0
equiv of pyrazole in this transformation. However, the reaction
Reaction Scope. The optimized catalytic condition shown
in entry 7 of Table 1 (10 mol % of AgNO3 in chlorobenzene at
80 °C) was finally selected in screening the reaction among a
series of propargyl acetates and pyrazole (2). The results are
summarized in Table 2. The electron-neutral 1-phenylprop-2-
ynyl acetate (1a) reacted with 2 to give 3a−5a in overall good
yields, with the isolation of 54% of 4a. The F/Cl groups at the
para position on the aryl moiety in 1b,c reacted effectively with
2, and the corresponding allyl acetates 3b,c and dipyrazolyl-
bearing compounds 4b,c and 5b,c were obtained in good
overall yields.
The reaction of propargyl acetates having electron-donating
methyl, methoxy, or phenoxy groups at the 4- and/or 3-
position on the aryl ring with 2 gave the corresponding ADPs
4d−f in 48%, 56%, and 63% yields, respectively. The free
phenol −OH moiety did not affect the reaction outcome, and
the corresponding phenol products 3g−5g were isolated in
83% overall yield. Although annulation between phenols and
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a b
,
Table 2. AgNO3-Catalyzed Reaction between Propargyl Acetates and Pyrazole (2)
a
b
Reactions were carried out using 1 (1.0 mmol), 2 (5.0 mmol), and AgNO3 (10 mol %) in chlorobenzene (1.0 mL) at 80 °C for 24 h. Isolated
c
d
yield. Deprotection of the acetyl group was observed. Reaction continued for 53 h.
propargyl alcohols in the presence of a Lewis acid is known to
furnish benzofurans,9 not even a trace amount of benzofuran
was observed by GC-MS analysis under the optimized reaction
conditions. Gratifyingly, the hydroxyl protecting groups O-
TBDMS and O-MOM survived during the reaction and the
corresponding products 3h−5h and 3i and 4i were obtained in
good yields.
Since phenolic esters are more labile than esters obtained
from alcohols,10 we expect cleavage of the phenol-O-acetate
group in this Ag-catalyzed transformation. As anticipated, the
acyl group was cleaved under the reaction conditions to afford
3g−5g. To investigate the effect of ortho substitution, o-methyl,
o-bromo, and o,p-dichloro groups on the aryl moiety in the
propargyl acetates were individually reacted with 2 and the
corresponding products 3k−5k, 3l and 4l, and 3m and 4m
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were isolated in 75%, 70% and 81% overall yields, respectively.
Moreover, the reaction between the sterically demanding 1-
(2,6-dichlorophenyl)-prop-2-ynyl acetate (1n) and 2 gave 3n
(12%) and 4n (51%) in overall moderate amounts. X-ray
crystallographic analysis unambiguously elucidated the struc-
ture of 4n.11 The 1-naphthyl-substituted ADP 4o was obtained
in 48% yield. The structures of 3o and 5o were confirmed on
the basis of X-ray crystallographic analysis.11 Generally,
coordination of the S heteroatom to the Lewis acid has a
negative impact on the reaction outcome.12 However, the
thienyl-2-substituted propargyl acetate 1p reacted with 2 under
the optimized conditions to afford 3p−5p, albeit in relatively
good isolated yields of 12%, 55%, and 7%, respectively. The
formyl group did not affect the reaction, delivering 4q and 3q in
54% and 19% yields, respectively. The optimized conditions
tolerate the labile 1,3-dioxolane protecting group, furnishing
3r−5r in 77% overall yield. The electron-rich methylenedioxy-
substituted propargyl acetate 1s reacted sluggishly with 2,
delivering 10%, 50%, and 17% of 3s−5s, respectively. However,
the reaction of alkylpropargyl acetate with 2 gave the
hydroamination products 3t and 3t′ (Scheme 2).2a
9 and 10 as pale yellow solids in 89% and 88% yields,
respectively (Scheme 4). The structure of 9 was confirmed on
the basis of an X-ray crystallographic analysis.11
Scheme 4. Complexation with PdCl2
To demonstrate the utility of the newly synthesized complex,
we explored examining this scorpionate-ligand-bearing Pd
complex 9/10 in the well-known Suzuki−Miyaura biaryl cross
coupling (Table 3).14 Gratifyingly, the electron-rich, electron-
Scheme 2. Reaction with Alkylpropargyl Acetate
Table 3. Suzuki Coupling between Various Aryl Halides and
Arylboronic Acids
a
Ar−Ar1 (13)
With the isolation of the products 3 and ADPs 4, the
hydrogenation of the double bond in 3 and 4 was next
investigated. For example, hydrogenation of 1-(naphthalen-1-
yl)-2-(1H-pyrazol-1-yl)allyl acetate (3o) with Pd/C in the
presence of an H2 balloon in MeOH furnished a mixture of an
equal amount of diastereomeric α-heteroarylated alcohol 7, a
key skeleton found in various azole-bearing antifungal agents13
(Scheme 3, eq 1). Similarly, 4a was hydrogenated under
b
entry
Ar−X (11)
Ar1−B(OH)2 (12)
yield (%)
c
1
2
3
4
5
6
4-MeOC6H4I (11a) PhB(OH)2 (12a)
4-F3CC6H4I (11b) 12a
97
c
72
c
2-MeC6H4I (11c)
12a
94
c
2-thienyl-I (11d)
12a
80
c
11a
11a
4-FC6H4B(OH)2 (12b)
95
c
3-MeC6H4B(OH)2
(12c)
86
c
7
8
9
11a
1-naphthyl-B(OH)2
(12d)
96
Scheme 3. Hydrogenation Reactions
c
4-MeOC6H4Br
(11e)
12a
12a
83
c
4-MeOC6H4Cl
(11f)
08
d
10
11
12
11a
11e
11f
12a
12a
12a
96
d
81
d
trace
a
Reactions were carried out using 11 (3.0 mmol), 12 (6.0 mmol),
catalyst 9/10 (0.1 mol %), and K2CO3 (6.0 mmol) in H2O (10.0 mL)
b
c
d
at 80 °C for 24 h. Isolated yield. Catalyst 9 was employed. Catalyst
10 was used.
identical conditions, producing the gem-dipyrazolyl alkane 8 in
98% yield (Scheme 3, eq 2). The gem-dipyrazolyl alkanes
exhibit anti-inflammatory actions.4
poor, sterically hindered, and heteroaryl iodides 11 were
effectively coupled with PhB(OH)2 (12a) under the influence
of 0.1 mol % of catalyst 9 in aqueous K2CO3 at 80 °C (entries
1−4). Similarly, the reaction of substituted boronic acids 12b−
d with 4-methoxyiodobenzene (11a) afforded the desired
biaryls in excellent yields (entries 5−7). Furthermore, 4-
methoxybromobenzene (11e) successufully coupled with 12a
under the influence of catalyst 9 (entry 8), while the coupling
of 4-methoxychlorobenzene (11f) with 12a gave 8% of the
desired biaryl (entry 9).
A wide array of the stereoselective scorpionate ligands (E)-
allyl-gem-dipyrazoles (ADPs) have been prepared from
propargyl acetates and pyrazole (Table 2). The presence of
two adjacent N atoms in the ADPs provides strong chelation
ability to the metal, allowing the formation of newly
synthesized scorpionate ligands. We therefore envisioned
examining the chelation ability of ADPs to the transition
metal. Gratifyingly, the reaction of 4o/8 with PdCl2 in CH3CN
at room temperature readily delivered the palladium complexes
We next explored the catalytic activity of a scorpionate ligand
having a reduced double bond and tethered phenyl group, Pd
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Scheme 5
voltage of 70 eV; data are reported in the form of m/z (intensity
relative to base peak 100). Elemental (C, H, N) analysis was carried
out using an EA 1112 analyzer. Melting points were determined on an
electro-thermal melting point apparatus and are uncorrected. X-ray
data were collected at 298 K using graphite-monochromated Mo Kα
radiation (0.71073 Å).
Preparation of 1″ from 1′: General Procedure GP-1 (Scheme
5). A solution of (trimethylsilyl)acetylene (1.2 equiv) in THF (50 mL)
was stirred in a 100 mL oven-dried two-necked round-bottom flask
under an argon atmosphere at −70 °C. n-Butyllithium (1.2 equiv, 1.60
M in THF) was introduced over 30 min at −70 °C. After an additional
1 h of stirring, a solution of the aldehyde (1′; 1.0 g, 1.0 equiv) in THF
(5 mL) was added at −70 °C. The resulting mixture was stirred for 1 h
and warmed to room temperature slowly, and the stirring was
continued for 30 min. The reaction mixture was quenched with
saturated NH4Cl aqueous solution (20 mL) at 0 °C. The organic layer
was separated; the aqueous layer was extracted with Et2O (2 × 20
mL). The combined extracts were washed with water (2 × 20 mL) and
brine (25 mL) and dried over Na2SO4. The solvent was filtered and
evaporated under the reduced pressure. The crude residue was
subsequently used for the desilylation reaction.
Methanol (15 mL) and K2CO3 (2.5 equiv) were introduced to the
crude residue obtained in the above reaction, and the heterogeneous
mixture was stirred under an argon atmosphere at ambient
temperature overnight. The reaction mixture was diluted with ethyl
acetate (50 mL) and washed with water (2 × 20 mL) and brine (10
mL). The organic layer was separated, dried over Na2SO4, filtered, and
concentrated under vacuum. In most cases the crude residue was used
for the acetylation reaction without purification, following the general
procedure GP 2.
complex 10, in the Suzuki−Miyaura couplings (entries 10−12,
Table 3). Gratifyingly, coupling of 4-methoxyiodo- and 4-
methoxybromobenzene (11a,e) with 12a successfully pro-
ceeded under the influence of catalyst 10, delivering 96% and
81% of the biaryl, respectively (entries 10 and 11). A trace
amount of the desired biaryl was detected in GC-MS when 4-
methoxychlorobenzene (11f) reacted with 12a in the presence
of catalyst 10 (entry 12).
On the basis of precedence and our observations, a plausible
reaction pathway is shown in Scheme 1.1o,2,15 Markovnikov
hydroamination of pyrazole to the Lewis acid activated triple
bond of propargyl acetate provides the 1-aryl-2-pyrazolyl allyl
acetate (path I).15b The attack of pyrazole at the terminal side
of the alkyne in the propargyl acetate possibly generates the
allene intermediate A with cleavage of the acetate moiety (path
II).21 Subsequently, addition of pyrazole at the α or γ position
of the transiently formed allene delivers ADPs 4 (major) and
1,3-dipyrazolyl-3-aryl propenes 5 (minor). The coordination of
pyrazole N and the β carbon of allene to the Ag(I) salt allows
the formation of the intermediate C.1j,22 The preferential attack
of pyrazole at the intermediate C generates 4 as the major
product. The lack of coordination of the aryl moiety to the Ag-
activated allene is presumably responsible for the formation of
the minor amount of 5. Alternatively, hydroamination of
pyrazole with 6 would lead to 5. Unfortunately, we did not even
observe a trace amount of 6 in this study, as the identical
compounds of 6 are found to be unstable in the Lewis acid
catalysts.2b
Synthesis of 1 from 1″ through Acylation of the −OH
Moiety: General Procedure GP-2. To a solution of 1″ (1.0 equiv)
and DMAP (0.1 equiv) in dichloromethane (15 mL) were added Et3N
(3 equiv) and acetic anhydride (1.3 equiv) under an argon atmosphere
at an ambient temperature. The resulting reaction mixture was stirred
for 1 h at an ambient temperature. Water (20 mL) was added to the
reaction mixture. The organic layer was separated; the aqueous layer
was extracted with CH2Cl2 (2 × 20 mL). The combined extracts were
washed with water (2 × 20 mL) and brine (25 mL) and dried over
Na2SO4. The solvent was filtered and evaporated under reduced
pressure. The crude residue was purified using column chromatog-
raphy on silica gel with hexane and ethyl acetate solvents as eluents.
Physical characterization data exactly match the reported values for
the respective compounds 1a−h,k−q,s,3a whereas data for 1i,j,r are
new.
CONCLUSION
■
In conclusion, we have demonstrated an Ag-catalyzed reaction
between propargyl acetate and pyrazole for the synthesis of
novel ADPs. The reaction also affords 1,2-disubstituted allyl
acetates 3 (10−25% yield) and 1,3-dipyrazolyl-3-aryl propenes
5 (6−17% yield), shows a broad substrate scope, and tolerates
various O-bearing labile protecting groups. The PdCl2-chelated
complex of ADPs was successfully employed in Suzuki
reactions for biaryl synthesis. Further investigation of the
synthetic applications of ADP−metal complexes is currently
underway.
1-(3-(Methoxymethoxy)phenyl)prop-2-ynyl Acetate (1i). Follow-
ing the general procedures GP-1 and GP-2, the reaction of 3-
(methoxymethoxy)benzaldehyde (1′i; 1.0 g, 6.02 mmol),
(trimethylsilyl)acetylene (0.71 g, 7.22 mmol), and n-BuLi (4.6 mL,
1.6 M in THF, 7.22 mmol) followed by desilylation gave the crude
product 1″i. Acetylation of the −OH moiety of the crude 1″i afforded
1-(3-(methoxymethoxy)phenyl)prop-2-ynyl acetate (1i; 775 mg) in
overall 55% yield as a pale yellow liquid: Rf = 0.71 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.31 (t, J =
8.0 Hz, 1H), 7.21 (bt, J = 2.0 Hz, 1H), 7.17 (d, J = 7.6 Hz, 1H), 7.06
(ddd, J = 8.4, 2.4, 0.8 Hz, 1H), 6.42 (bd, J = 2.0 Hz, 1H), 5.20 (bs,
2H), 3.49 (s, 3H), 2.66 (bd, J = 2.0 Hz, 1H), 2.13 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 169.5, 157.3, 137.8, 129.7, 121.0, 116.6, 115.6,
94.3, 80.0, 75.4, 64.9, 55.9, 20.9; IR (neat) νmax 3287, 2957, 2125,
1743, 1601, 1226, 696 cm−1; MS (EI) m/z (%) 235 (M+ + 1, 100),
220 (3). Anal. Calcd for C13H14O4: C, 66.66; H, 6.02. Found: C,
66.72; H, 6.15.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all of the reagents
and intermediates were obtained commercially and used without
purification. Dichloromethane (DCM) and chlorobenzene were
distilled over CaCl2. THF was freshly distilled over sodium/
benzophenone ketyl under dry nitrogen. Methanol was dried over
magnesium cake. Analytical and spectral data of all those known
compounds exactly match the reported values.
Proton and carbon nuclear magnetic resonance spectra (1H NMR,
13C NMR, and 19F NMR) were recorded on 400 MHz (1H NMR, 400
MHz; 13C NMR, 101 MHz; 19F NMR, 376 MHz) and 500 MHz
spectrometers (1H NMR, 500 MHz; 13C NMR, 126 MHz; 19F NMR,
470 MHz) with the solvent resonance as internal standard (1H NMR,
CHCl3 at 7.26 ppm; 13C NMR, CDCl3 at 77.0 ppm). In a few cases
tetramethylsilane (TMS) at 0.00 ppm was used as the reference
standard. IR spectra were recorded and reported in cm−1. LC-MS
spectra were obtained (EI positive/negative mode) with an ionization
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1-(3-Acetoxyphenyl)prop-2-ynyl Acetate (1j). Following the
general procedure GP-1 and GP-2, reaction of 3-((tert-
butyldimethylsilyl)oxy)benzaldehyde (1′j; 1.0 g, 4.24 mmol),
(trimethylsilyl)acetylene (498 mg, 5.07 mmol), and n-BuLi (3.2 mL,
1.6 M in THF, 5.08 mmol) gave the crude propargylic alcohol.
Desilylation and acetylation of both −OH moieties afforded 1-(3-
acetoxyphenyl)prop-2-ynyl acetate (1j; 462 mg) in 47% overall yield as
a pale yellow oil: Rf = 0.11 (9/1 hexane/EtOAc) [silica, UV and I2];
1H NMR (400 MHz, CDCl3) δ 7.43−7.36 (m, 2H), 7.27 (s, 1H), 7.10
(bd, J = 2.8 Hz, 1H), 6.44 (s, 1H), 2.67 (bs, 1H), 2.28 (s, 3H), 2.09 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 169.4, 169.1, 150.6, 137.8,
129.5, 124.9, 122.2, 120.8, 79.6, 75.6, 64.4, 20.9, 20.8; IR (neat) νmax
3288, 2935, 1739, 1201, 1016, 800 cm−1; MS (EI) m/z (%) 255 (M+ +
Na, 100), 232 (M+, 4), 173 (8). Anal. Calcd for C13H12O4: C, 67.23;
H, 5.21. Found: C, 67.35; H, 5.18.
− 1, 100), 237 (14), 209 (4). Anal. Calcd for C15H14N4: C, 71.98; H,
5.64; N, 22.38. Found: C, 71.86; H, 5.61; N, 22.45.
(E)-1,1′-(3-(4-Fluorophenyl)prop-2-ene-1,1-diyl)bis(1H-pyrazole)
(4b): pale yellow solid (145 mg, 54% yield); mp 60−61 °C; Rf = 0.44
(3/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 7.65 (bd, J = 2.0 Hz, 2H), 7.59 (bd, J = 1.6 Hz, 2H), 7.34
(dd, J = 8.8, 5.6 Hz, 2H), 7.18 (d, J = 6.0, 1H), 6.97 (t, J = 8.8 Hz,
2H), 6.84 (dd, J = 16.0, 6.4 Hz, 1H), 6.51 (d, J = 16.0 Hz, 1H), 6.29 (t,
J = 2.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 162.7 (d, J = 250
Hz), 140.3, 134.2, 131.0, 128.6, 128.5, 122.2, 115.4 (d, J = 21.7 Hz),
106.5, 75.9; 19F NMR (376 MHz, CDCl3) δ −112.26 to −112.34 (m);
IR (KBr) νmax 3115, 2924, 1678, 1510, 1394, 1226, 752 cm−1; MS (EI)
m/z (%) 269 (M+ + 1, 100), 186 (11), 137 (19), 91 (4). Anal. Calcd
for C15H13FN4: C, 67.15; H, 4.88; N, 20.88. Found: C, 67.22; H, 4.81;
N, 20.75.
1-(4-Fluorophenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3b): pale
yellow semisolid (52 mg, 20% yield); Rf = 0.66 (3/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J
= 2.4 Hz, 1H), 7.56 (bd, J = 1.2 Hz, 1H), 7.46−7.37 (m, 2H), 7.09 (s,
1H), 7.00 (t, J = 8.8 Hz, 2H), 6.26 (bt, J = 2.0 Hz, 1H), 5.52 (s, 1H),
5.11 (s, 1H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.3,
162.7 (d, J = 248 Hz), 144.2, 140.7, 132.9, 129.3 (d, J = 8.4 Hz), 127.8,
115.5 (d, J = 21.6 Hz) 107.0, 102.9, 72.4, 21.0; 19F NMR (376 MHz,
CDCl3) δ −113.07 to −113.14 (m); IR (neat) νmax 3128, 1747, 1510,
1224, 752 cm−1; MS (EI) m/z (%) 261 (M+ + 1, 100), 233 (54), 219
(14), 201 (16), 113 (9). Anal. Calcd for C14H13FN2O2: C, 64.61; H,
5.03; N, 10.76. Found: C, 64.48; H, 5.10; N, 10.85.
1-(4-(1,3-Dioxan-2-yl)phenyl)prop-2-ynyl Acetate (1r). Following
the general procedure GP-1 and GP-2, reaction of 4-(1,3-dioxan-2-
yl)benzaldehyde (1′r; 1.0 g, 5.21 mmol), (trimethylsilyl)acetylene
(0.61 g, 6.25 mmol), and n-BuLi (4.0 mL, 1.6 M in THF, 6.25 mmol)
followed by desilylation gave the crude product 1″r. Acetylation of the
−OH moiety of the crude 1″r afforded 1-(4-(1,3-dioxan-2-yl)phenyl)-
prop-2-ynyl acetate (1r; 840 mg) in 62% overall yield as a colorless
1
liquid: Rf = 0.69 (3/1 hexane/EtOAc) [silica, UV and I2]; H NMR
(400 MHz, CDCl3) δ 7.59−7.49 (m, 4H), 6.45 (bd, J = 2.4 Hz, 1H),
5.51 (s, 1H), 4.27 (dd, J = 11.2, 5.2 Hz, 2H), 3.99 (td, J = 12.0, 2.4 Hz,
2H), 2.64 (bd, J = 2.0 Hz, 1H), 2.30−2.15 (m, 1H), 2.09 (s, 3H), 1.46
(dd, J = 13.6, 1.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 169.5,
139.5, 136.8, 127.5, 126.3, 100.9, 80.0, 75.4, 67.2, 64.9, 25.6, 20.9; IR
(neat) νmax 3287, 2966, 1741, 1377, 1016, 642 cm−1; MS (EI) m/z
(%) 261 (M+ + 1, 100), 247 (5), 245 (5). Anal. Calcd for C15H16O4:
C, 69.22; H, 6.20. Found: C, 69.06; H, 6.27.
Silver(I)-Catalyzed Reaction between Pyrazole (2) and
Propargyl Acetates 1: General Procedure GP-3. Propargyl
acetate 1 (1.0 mmol), pyrazole (5.0 mmol), and AgNO3 (16.9 mg,
0.1 mmol) were placed in an oven-dried Schlenk flask under an argon
atmosphere. Chlorobenzene (1.0 mL) was added to this mixture. The
resulting solution was stirred at 80 °C for 24 h. Upon complete
consumption of 1, the crude reaction mixture was purified using
column chromatography on silica gel with hexane and ethyl acetate
solvents as eluents.
(E)-1,1′-(3-Phenylprop-2-ene-1,1-diyl)bis(1H-pyrazole) (4a): color-
less solid (135 mg, 54% yield); mp 94−95 °C; Rf = 0.30 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.69 (bd, J
= 2.4 Hz, 2H), 7.63 (bd, J = 1.6 Hz, 2H), 7.43 (d, J = 7.6 Hz, 2H),
7.36−7.27 (m, 3H), 7.23 (d, J = 6.4 Hz, 1H), 6.95 (dd, J = 15.6, 6.0
Hz, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.33 (bt, J = 1.6 Hz, 2H); 13C
NMR (101 MHz, CDCl3) δ 140.3, 135.5, 134.9, 128.6, 128.5, 128.4,
126.9, 122.4, 106.5, 76.0; IR (KBr) νmax 3109, 1392, 1296, 970, 754,
628 cm−1; MS (EI) m/z (%) 249 (M+−1, 100), 229 (54), 211 (35),
171 (35), 134 (19), 113 (27). Anal. Calcd for C15H14N4: C, 71.98; H,
5.64; N, 22.38. Found: C, 72.05; H, 5.71; N, 22.31.
1-Phenyl-2-(1H-pyrazol-1-yl)allyl acetate (3a): pale yellow oil (61
mg, 25% yield); Rf = 0.53 (4/1 hexane/EtOAc) [silica, UV and I2]; 1H
NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 5.6, 2.4 Hz, 2H), 7.44 (dd, J
= 8.0, 1.6 Hz, 2H), 7.37−7.29 (m, 3H), 7.12 (s, 1H), 6.27 (t, J = 2.0
Hz, 1H), 5.58 (bd, J = 0.8 Hz, 1H), 5.11 (s, 1H), 2.14 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 169.3, 144.0, 140.5, 136.8, 128.5, 127.8,
127.2, 106.8, 103.3, 73.1, 21.0; IR (neat) νmax 3474, 2932, 1745, 1226,
949, 752 cm − 1; MS (EI) m/z (%) 243 (M+ + 1, 100), 159 (3), 137
(3), 81 (3). Anal. Calcd for C14H14N2O2: C, 69.41; H, 5.82; N, 11.56.
Found: C, 69.75; H, 6.12; N, 11.15.
(E)-1,1′-(3-(4-Fluorophenyl)prop-1-ene-1,3-diyl)bis(1H-pyrazole)
(5b): yellow oil (21 mg, 8% yield); Rf = 0.31 (3/1 hexane/EtOAc)
1
[silica, UV and I2]; H NMR (400 MHz, CDCl3) δ 7.63 (bd, J = 2.0
Hz, 1H), 7.61 (bd, J = 2.0 Hz, 1H), 7.56 (d, J = 2.4 Hz, 1H), 7.49 (d, J
= 2.4 Hz, 1H), 7.26−7.17 (m, 2H), 7.10−7.03 (m, 2H), 6.82 (dd, J =
14.0, 0.8 Hz, 1H), 6.66 (dd, J = 14.0, 6.8 Hz, 1H), 6.37 (t, J = 2.0 Hz,
1H), 6.33 (t, J = 2.4 Hz, 1H), 6.19 (d, J = 6.8 Hz, 1H); 13C NMR (101
MHz, CDCl3) δ 162.5 (d, J = 248 Hz), 141.5, 139.9, 134.7 (d, J = 3.2
Hz), 130.6, 129.1 (d, J = 8.5 Hz), 128.4 (2c), 115.8 (d, J = 21.9 Hz),
114.7, 107.5, 106.0, 64.4; 19F NMR (376 MHz, CDCl3) δ −113.53 to
−113.60 (m); IR (neat) νmax 2924, 1678, 1510, 1394, 1226, 752 cm−1;
MS (EI) m/z (%) 269 (M+ + 1, 19), 201 (100), 113 (14). Anal. Calcd
for C15H13FN4: C, 67.15; H, 4.88; N, 20.88. Found: C, 67.06; H, 4.91;
N, 20.95.
(E)-1,1′-(3-(4-Chlorophenyl)prop-2-ene-1,1-diyl)bis(1H-pyrazole)
(4c): pale yellow solid (153 mg, 54% yield); mp 111−112 °C; Rf =
1
0.44 (3/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz,
CDCl3) δ 7.64 (bd, J = 2.4 Hz, 2H), 7.59 (bd, J = 2.0 Hz, 2H), 7.28 (q,
J = 8.4 Hz, 4H), 7.18 (dd, J = 6.0, 0.8 Hz, 1H), 6.89 (dd, J = 16.0, 6.0
Hz, 1H), 6.49 (d, J = 16.0 Hz, 1H), 6.30 (bt, J = 2.0 Hz, 2H); 13C
NMR (101 MHz, CDCl3) δ 140.4, 134.3, 134.1, 133.4, 128.7, 128.5,
128.1, 123.2, 106.6, 75.9; IR (KBr) νmax 3099, 1390, 1089, 750 cm−1;
MS (EI) m/z (%) 286 (M+ + 1, 100), 230 (21), 208 (4), 190 (6).
Anal. Calcd for C15H13ClN4: C, 63.27; H, 4.60; N, 19.68. Found: C,
63.41; H, 4.53; N, 19.58.
1-(4-Chlorophenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3c): yellow
oil (52 mg, 19% yield); Rf = 0.66 (3/1 hexane/EtOAc) [silica, UV and
I2]; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 2.4 Hz, 1H), 7.57 (d, J
= 1.6 Hz, 1H), 7.37 (dt, J = 8.8, 2.0 Hz, 2H), 7.29 (dt, J = 8.4, 2.0 Hz,
2H), 7.08 (s, 1H), 6.27 (bt, J = 2.4 Hz, 1H), 5.51 (bd, J = 1.2 Hz, 1H),
5.11 (s, 1H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.2,
143.9, 140.6, 135.5, 134.4, 128.8, 128.7, 127.7, 107.0, 102.9, 72.4, 20.9;
IR (neat) νmax 3128, 2928, 1745, 1651, 1228, 752 cm−1; MS (EI) m/z
(%) 277 (M+, 94), 249 (49), 217 (100), 183 (29), 149 (6). Anal.
Calcd for C14H13ClN2O2: C, 60.77; H, 4.74; N, 10.12. Found: C,
60.61; H, 4.71; N, 10.18.
(E)-1,1′-(3-Phenylprop-1-ene-1,3-diyl)bis(1H-pyrazole) (5a): yel-
low oil (23 mg, 9% yield); Rf = 0.23 (4/1 hexane/EtOAc) [silica, UV
and I2]; 1H NMR (400 MHz, CDCl3) δ 7.62 (dd, J = 4.8, 1.6 Hz, 2H),
7.56 (d, J = 2.4 Hz, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.41−7.27 (m, 5H),
6.85 (dd, J = 14.0, 0.8 Hz, 1H), 6.69 (dd, J = 14.0, 7.2 Hz, 1H), 6.36 (t,
J = 2.0 Hz, 1H), 6.33 (t, J = 2.0 Hz, 1H), 6.22 (d, J = 7.2 Hz, 1H); 13C
NMR (101 MHz, CDCl3) δ 141.3, 139.7, 138.8, 130.5, 128.9, 128.5,
128.34, 128.31, 127.3, 114.9, 107.4, 105.8, 65.1; IR (neat) νmax 3433,
3113, 2924, 1680, 1394, 1091, 750 cm−1; MS (EI) m/z (%) 249 (M+
(E)-1,1′-(3-(4-Chlorophenyl)prop-1-ene-1,3-diyl)bis(1H-pyrazole)
(5c): yellow oil (17 mg, 6% yield); Rf = 0.31 (3/1 hexane/EtOAc)
[silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 1.6 Hz,
1H), 7.60 (d, J = 1.6 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.49 (d, J = 2.4
Hz, 1H), 7.34 (dt, J = 8.4, 2.0 Hz, 2H), 7.17 (dt, J = 8.4, 1.6 Hz, 2H),
6.83 (d, J = 14.4 Hz, 1H), 6.64 (dd, J = 14.0, 7.2 Hz, 1H), 6.36 (t, J =
2.0 Hz, 1H), 6.32 (t, J = 2.4 Hz, 1H), 6.17 (d, J = 6.8 Hz, 1H); 13C
11829
dx.doi.org/10.1021/jo401867e | J. Org. Chem. 2013, 78, 11824−11834

The Journal of Organic Chemistry
Article
NMR (101 MHz, CDCl3) δ 141.5, 140.6, 140.0, 137.4, 134.3, 130.8,
129.1, 128.6, 128.5, 114.4, 107.5, 106.0, 64.5; IR (neat) νmax 3113,
2924, 1678, 1394, 1091, 752 cm−1; MS (EI) m/z (%) 286 (M+ + 1,
20), 285 (M+, 40), 233 (40), 217 (100), 181 (40), 149 (35). Anal.
Calcd for C15H13ClN4: C, 63.27; H, 4.60; N, 19.68. Found: C, 63.35;
H, 4.65; N, 19.55.
3H); 13C NMR (101 MHz, CDCl3) δ 160.0, 141.3, 140.4, 139.7,
130.7, 129.9, 128.5, 128.3, 119.6, 114.8, 113.7, 113.2, 107.4, 105.9,
65.1, 55.3; IR (neat) νmax 3117, 2932, 1678, 1601, 1261, 1043, 754
cm−1; MS (EI) m/z (%) 281 (M+ + 1, 100), 249 (8), 171 (4). Anal.
Calcd for C16H16N4O: C, 68.55; H, 5.75; N, 19.99. Found: C, 68.41;
H, 5.71; N, 19.85.
(E)-1,1′-(3-p-Tolylprop-2-ene-1,1-diyl)bis(1H-pyrazole) (4d): pale
(E)-1,1′-(3-(3-Phenoxyphenyl)prop-2-ene-1,1-diyl)bis(1H-pyra-
yellow solid (127 mg, 48% yield); mp 79−80 °C; Rf = 0.44 (4/1
zole) (4f): pale yellow solid (215 mg, 63% yield); mp 75−76 °C; Rf =
1
1
hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ
0.35 (6/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz,
7.67 (bd, J = 2.4 Hz, 2H), 7.61 (bd, J = 2.0 Hz, 2H), 7.32 (d, J = 8.0
Hz, 2H), 7.19 (dd, J = 6.0, 1.2 Hz, 1H), 7.14 (d, J = 8.0 Hz, 2H), 6.88
(dd, J = 16.0, 6.4 Hz, 1H), 6.58 (d, J = 16.4 Hz, 1H), 6.31 (bt, J = 2.4
Hz, 2H), 2.34 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 140.4, 138.7,
135.6, 132.2, 129.3, 128.5, 126.9, 121.4, 106.5, 76.2, 21.1; IR (KBr)
νmax 2916, 1512, 1388, 972, 758 cm−1; MS (EI) m/z (%) 265 (M+ + 1,
100), 251 (11). Anal. Calcd for C16H16N4: C, 72.70; H, 6.10; N, 21.20.
Found: C, 72.58; H, 6.15; N, 21.07.
CDCl3) δ 7.66 (bd, J = 2.8 Hz, 2H), 7.61 (bd, J = 1.2 Hz, 2H), 7.38−
7.25 (m, 3H), 7.19 (dd, J = 12.8, 6.0 Hz, 2H), 7.14−7.08 (m, 2H),
7.02 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 7.2 Hz, 1H), 6.91 (dd, J = 16.0,
6.0 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.31 (s, 2H); 13C NMR (101
MHz, CDCl3) δ 157.3, 156.8, 140.4, 136.8, 134.8, 129.8, 129.6, 128.5,
123.3, 123.2, 121.9, 119.1, 118.6, 117.2, 106.6, 75.9; IR (KBr) νmax
3109, 1577, 1388, 1271, 750 cm−1; MS (EI) m/z (%) 343 (M+ + 1, 3),
275 (38), 243 (100), 242 (27), 207 (14), 130 (8). Anal. Calcd for
C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found: C, 73.57; H, 5.36; N,
16.25.
1-(3-Phenoxyphenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3f): pale
yellow oil (63 mg, 19% yield); Rf = 0.56 (6/1 hexane/EtOAc) [silica,
UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 2.0 Hz, 1H),
7.60 (bd, J = 0.8 Hz, 1H), 7.38−7.33 (m, 2H), 7.30 (t, J = 6.4 Hz, 1H),
7.18 (d, J = 6.4 Hz, 1H), 7.15−7.09 (m, 3H), 6.98 (bt, J = 0.8 Hz, 1H),
6.97 (bt, J = 0.8 Hz, 1H), 6.96−6.92 (m, 1H), 6.30 (t, J = 1.6 Hz, 1H),
5.55 (bd, J = 0.8 Hz, 1H), 5.11 (s, 1H), 2.15 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 169.3, 157.4, 156.9, 144.1, 140.6, 139.0, 129.9, 129.8,
127.9, 123.4, 122.1, 118.9, 118.7, 117.7, 106.9, 103.5, 72.8, 21.0; IR
(neat) νmax 3065, 2930, 1747, 1585, 1234, 1024, 754 cm−1; MS (EI)
m/z (%) 336 (M+ + 2, 51), 335 (M+ + 1, 100), 263 (11). Anal. Calcd
for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.68; H, 5.52;
N, 8.31.
2-(1H-Pyrazol-1-yl)-1-p-tolylallyl acetate (3d): pale yellow solid
(56 mg, 22% yield); mp 60−61 °C; Rf = 0.62 (4/1 hexane/EtOAc)
1
[silica, UV and I2]; H NMR (400 MHz, CDCl3) δ 7.60−7.56 (m,
2H), 7.31 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.04 (s, 1H),
6.26 (bt, J = 2.4 Hz, 1H), 5.58 (s, 1H), 5.10 (s, 1H), 2.32 (s, 3H), 2.13
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.4, 144.1, 140.5, 138.4,
133.8, 129.2, 127.8, 127.3, 106.8, 103.1, 73.0, 21.1, 21.0; IR (KBr) νmax
3026, 2924, 1745, 1228, 1028, 752 cm−1; MS (EI) m/z (%) 257 (M+ +
1, 100), 239 (8), 157 (16), 133 (16), 85 (8). Anal. Calcd for
C15H16N2O2: C, 70.29; H, 6.29; N, 10.93. Found: C, 70.38; H, 6.21;
N, 10.85.
(E)-1,1′-(3-p-Tolylprop-1-ene-1,3-diyl)bis(1H-pyrazole) (5d): yel-
low oil (37 mg, 14% yield); Rf = 0.29 (4/1 hexane/EtOAc) [silica, UV
1
and I2]; H NMR (400 MHz, CDCl3) δ 7.60 (bd, J = 6.4 Hz, 2H),
7.53 (bd, J = 2.0 Hz, 1H), 7.45 (bd, J = 2.0 Hz, 1H), 7.16 (bd, J = 2.0
Hz, 4H), 6.82 (d, J = 14.0 Hz, 1H), 6.66 (dd, J = 14.0, 6.8 Hz, 1H),
6.32 (d, J = 17.2 Hz, 2H), 6.16 (d, J = 6.8 Hz, 1H), 2.34 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 141.2, 139.6, 138.1, 135.7, 130.3, 129.5,
128.4, 128.2, 127.2, 115.1, 107.3, 105.7, 64.8, 21.0; IR (neat) νmax
3111, 2922, 1678, 1514, 1089, 754 cm−1; MS (EI) m/z (%) 265 (M+ +
1, 100), 197 (3), 147 (3). Anal. Calcd for C16H16N4: C, 72.70; H, 6.10;
N, 21.20. Found: C, 72.85; H, 6.03; N, 21.28.
(E)-1,1′-(3-(3-Phenoxyphenyl)prop-1-ene-1,3-diyl)bis(1H-pyra-
zole) (5f): yellow oil (21 mg, 6% yield); Rf = 0.20 (6/1 hexane/
1
EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ 7.62 (bs,
1H), 7.60 (bd, J = 1.6 Hz, 1H), 7.56 (bd, J = 2.4 Hz, 1H), 7.51 (bd, J =
2.4 Hz, 1H), 7.37−7.28 (m, 3H), 7.11 (td, J = 7.6, 1.6 Hz, 1H), 7.01−
6.86 (m, 6H), 6.64 (dd, J = 14.0, 7.2 Hz, 1H), 6.36 (bt, J = 2.4 Hz,
1H), 6.32 (bt, J = 2.4 Hz, 1H), 6.17 (d, J = 7.2 Hz, 1H); 13C NMR
(101 MHz, CDCl3) δ 157.8, 156.7, 141.4, 141.0, 139.8, 130.8, 130.2,
129.8, 128.5, 128.3, 123.6, 121.8, 119.1, 118.2, 117.7, 114.5, 107.5,
105.9, 64.9; IR (neat) νmax 2922, 1678, 1583, 1487, 1248, 752 cm−1;
MS (EI) m/z (%) 343 (M+ + 1, 100), 209 (6), 135 (3). Anal. Calcd for
C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found: C, 73.56; H, 5.38; N,
16.21.
(E)-1,1′-(3-(3-Methoxyphenyl)prop-2-ene-1,1-diyl)bis(1H-pyra-
zole) (4e): pale yellow solid (157 mg, 56% yield); mp 97−98 °C; Rf =
1
0.24 (4/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz,
CDCl3) δ 7.68 (bd, J = 2.4 Hz, 2H), 7.61 (bd, J = 1.6 Hz, 2H), 7.29
−7.19 (m, 2H), 7.02 (d, J = 7.6 Hz, 1H), 6.99−6.90 (m, 2H), 6.85
(dd, J = 8.4, 2.0 Hz, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (bt, J = 2.4
Hz, 2H), 3.79 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 159.7, 140.4,
136.3, 135.5, 129.5, 128.6, 122.7, 119.6, 114.5, 112.0, 106.5, 76.0, 55.1;
IR (KBr) νmax 3111, 2957, 1599, 1390, 1043, 754 cm−1; MS (EI) m/z
(%) 281 (M+ + 1, 100), 265 (14), 163 (4), 137 (14). Anal. Calcd for
C16H16N4O: C, 68.55; H, 5.75; N, 19.99. Found: C, 68.47; H, 5.82; N,
19.85.
1-(3-Methoxyphenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3e): color-
less oil (65 mg, 24% yield); Rf = 0.43 (4/1 hexane/EtOAc) [silica, UV
and I2]; 1H NMR (400 MHz, CDCl3) δ 7.62−7.58 (m, 2H), 7.25 (t, J
= 8.0 Hz, 1H), 7.08 (s, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.97 (bt, J = 2.0
Hz, 1H), 6.84 (ddd, J = 8.0, 2.4, 0.8 Hz, 1H), 6.27 (t, J = 2.0 Hz, 1H),
5.57 (d, J = 0.8 Hz, 1H), 5.11 (s, 1H), 3.78 (s, 3H), 2.15 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 169.3, 159.6, 144.0, 140.5, 138.4, 129.5,
127.8, 119.4, 113.8, 112.9, 106.8, 103.4, 72.9, 55.1, 21.0; IR (neat) νmax
3130, 2939, 1747, 1602, 1228, 1030, 754 cm−1; MS (EI) m/z (%) 273
(M+ + 1, 82), 245 (36), 229 (54), 213 (100), 145 (7), 102 (5). Anal.
Calcd for C15H16N2O3: C, 66.16; H, 5.92; N, 10.29. Found: C, 66.32;
H, 5.86; N, 10.15.
(E)-3-(3,3-Bis(1H-pyrazol-1-yl)prop-1-enyl)phenol (4g): light
brown solid (122 mg, 46% yield); mp 100−101 °C; Rf = 0.34 (2/1
1
hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ
7.64 (bd, J = 2.0 Hz, 2H), 7.61 (bd, J = 1.2 Hz, 2H), 7.12 (dd, J = 5.2,
0.8 Hz, 1H), 7.09 (d, J = 6.4 Hz, 1H), 6.86 (d, J = 6.4 Hz, 1H), 6.83−
6.79 (m, 1H), 6.78 (d, J = 4.8 Hz, 1H), 6.77−6.73 (m, 1H), 6.43 (d, J
= 12.8 Hz, 1H), 6.31 (t, J = 2.0 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ 156.6, 140.6, 136.4, 136.0, 129.8, 129.0, 122.2, 119.2, 116.3,
114.0, 106.8, 76.1; IR (KBr) νmax 3142, 2729, 1595, 1392, 1089, 756
cm−1; MS (EI) m/z (%) 268 (M+ + 2, 100), 156 (14). Anal. Calcd for
C15H14N4O: C, 67.65; H, 5.30; N, 21.04. Found: C, 67.49; H, 5.26; N,
21.15.
1-(3-Hydroxyphenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3g): brown
oil (59 mg, 23% yield); Rf = 0.53 (2/1 hexane/EtOAc) [silica, UV and
1
I2]; H NMR (400 MHz, CDCl3) δ 7.59 (bd, J = 2.0 Hz, 1H), 7.58
(bd, J = 1.2 Hz, 1H), 7.18 (t, J = 6.0 Hz, 1H), 6.98 (s, 1H), 6.95 (d, J =
6.4 Hz, 1H), 6.88 (bt, J = 1.6 Hz, 1H), 6.79−6.74 (m, 1H), 6.27 (t, J =
1.6 Hz, 1H), 5.57 (bd, J = 0.8 Hz, 1H), 5.12 (s, 1H), 2.12 (s, 3H),
1.90−1.70 (bs, 1H); 13C NMR (101 MHz, CDCl3) δ 169.6, 156.1,
143.7, 140.6, 138.3, 129.8, 128.2, 119.2, 115.8, 114.3, 106.9, 104.4,
73.0, 21.0; IR (neat) νmax 3333, 2926, 1747, 1593, 1228, 760 cm−1; MS
(EI) m/z (%) 260 (M+ + 2, 100), 163 (6). Anal. Calcd for
C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.21; H, 5.41;
N, 10.76.
(E)-1,1′-(3-(3-Methoxyphenyl)prop-1-ene-1,3-diyl)bis(1H-pyra-
zole) (5e): yellow oil (17 mg, 6% yield); Rf = 0.14 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.63 (bd, J
= 1.2 Hz, 1H), 7.62 (bd, J = 1.6 Hz, 1H), 7.57 (d, J = 2.0 Hz, 1H),
7.51 (d, J = 2.0 Hz, 1H), 7.32−7.27 (m, 1H), 6.89−6.84 (m, 3H), 6.78
(bt, J = 1.6 Hz, 1H), 6.67 (dd, J = 11.2, 5.6 Hz, 1H), 6.37 (t, J = 1.6
Hz, 1H), 6.33 (t, J = 1.6 Hz, 1H), 6.18 (d, J = 5.6 Hz, 1H), 3.79 (s,
11830
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The Journal of Organic Chemistry
Article
(E)-3-(1,3-Bis(1H-pyrazol-1-yl)allyl)phenol (5g): brown oil (37 mg,
14% yield); Rf = 0.22 (2/1 hexane/EtOAc) [silica, UV and I2]; H
169.3, 157.3, 143.9, 140.5, 138.4, 129.5, 127.8, 120.7, 116.0, 115.3,
106.8, 103.6, 94.4, 72.8, 55.9, 21.0; IR (neat) νmax 2925, 1747, 1588,
1221, 767 cm−1; MS (EI) m/z (%) 303 (M+ + 1, 100), 282 (11), 215
(8), 79 (24). Anal. Calcd for C16H18N2O4: C, 63.56; H, 6.00; N, 9.27.
Found: C, 63.42; H, 6.15; N, 9.31.
Following the general procedure GP-3, 1-(3-acetoxyphenyl)prop-2-
ynyl acetate (1j; 232 mg, 1.0 mmol), pyrazole (2; 340 mg, 5.0 mmol),
and AgNO3 (16.9 mg, 0.1 mmol) in chlorobenzene (1.0 mL) were
heated at 80 °C for 24 h. Finally, the crude mixture was purified by
silica gel column chromatography with hexane/ethyl acetate (2/1) as
eluent to afford the acetyl deprotected compounds 3g (52 mg) in 20%
yield as a brown oil, 4g (135 mg) in 51% yield as a light brown solid,
and 5g (29 mg) in 11% yield as a brown oil.
1
NMR (400 MHz, CDCl3) δ 9.35−8.35 (bs, 1H), 7.61 (bd, J = 1.6 Hz,
1H), 7.54 (bd, J = 1.6 Hz, 1H), 7.51 (bd, J = 2.4 Hz, 1H), 7.49 (bd, J =
2.4 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.79 (d, J = 14.0 Hz, 1H), 6.66
(t, J = 8.0 Hz, 2H), 6.57 (dd, J = 14.0, 7.2 Hz, 1H), 6.48 (s, 1H), 6.34
(bt, J = 2.0 Hz, 1H), 6.28 (bt, J = 2.0 Hz, 1H), 6.07 (d, J = 7.2 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 157.2, 141.3, 139.8, 139.5,
130.8, 129.9, 129.0, 128.7, 118.4, 115.8, 114.6, 114.1, 107.5, 105.9,
64.8; IR (neat) νmax 3146, 2928, 1678, 1601, 1282, 945, 653 cm−1; MS
(EI) m/z (%) 268 (M+ + 2, 30), 267 (M+ + 1, 100), 235 (81). Anal.
Calcd for C15H14N4O: C, 67.65; H, 5.30; N, 21.04. Found: C, 67.48;
H, 5.21; N, 21.15.
(E)-1,1′-(3-o-Tolylprop-2-ene-1,1-diyl)bis(1H-pyrazole) (4k): color-
less solid (100 mg, 38% yield); mp 73−74 °C; Rf = 0.33 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J
= 2.4 Hz, 2H), 7.62 (bd, J = 1.6 Hz, 2H), 7.53 (dd, J = 6.8, 2.4 Hz,
1H), 7.25−7.09 (m, 4H), 6.83 (bd, J = 2.8 Hz, 2H), 6.33 (t, J = 2.0 Hz,
2H), 2.29 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 140.4, 135.9,
134.0, 133.4, 130.3, 128.5, 126.1, 125.9, 123.6, 106.5, 76.2, 19.5; IR
(KBr) νmax 3109, 2986, 1510, 1392, 754 cm−1; MS (EI) m/z (%) 265
(M+ + 1, 100), 251 (12). Anal. Calcd for C16H16N4: C, 72.70; H, 6.10;
N, 21.20. Found: C, 72.59; H, 6.18; N, 21.32.
(E)-1,1′-(3-(3-(tert-Butyldimethylsilyloxy)phenyl)prop-2-ene-1,1-
diyl)bis(1H-pyrazole) (4h): colorless solid (186 mg, 49% yield); mp
1
62−63 °C; Rf = 0.53 (4/1 hexane/EtOAc) [silica, UV and I2]; H
NMR (400 MHz, CDCl3) δ 7.67 (bd, J = 2.4 Hz, 2H), 7.60 (bd, J =
1.6 Hz, 2H), 7.19 (t, J = 7.6 Hz, 2H), 7.03 (d, J = 7.6 Hz, 1H), 6.94−
6.86 (m, 2H), 6.79 (dd, J = 8.0, 2.4 Hz, 1H), 6.54 (d, J = 15.6 Hz, 1H),
6.31 (bd, J = 1.6 Hz, 2H), 1.00 (s, 9H), 0.20 (s, 6H); 13C NMR (101
MHz, CDCl3) δ 155.7, 140.4, 136.4, 135.4, 129.4, 128.5, 122.5, 120.3,
120.1, 118.6, 106.5, 76.0, 25.5, 18.0, −4.5; IR (KBr) νmax 3109, 1595,
1280, 966, 621 cm−1; MS (EI) m/z (%) 381 (M+ + 1, 100), 203 (3),
106 (6). Anal. Calcd for C21H28N4OSi: C, 66.28; H, 7.42; N, 14.72.
Found: C, 66.42; H, 7.35; N, 14.61.
2-(1H-Pyrazol-1-yl)-1-o-tolylallyl acetate (3k): yellow oil (69 mg,
1
27% yield); Rf = 0.57 (4/1 hexane/EtOAc) [silica, UV and I2]; H
NMR (400 MHz, CDCl3) δ 7.63 (d, J = 2.4 Hz, 1H), 7.59 (bd, J = 1.6
Hz, 1H), 7.42 (dd, J = 6.8, 2.0 Hz, 1H), 7.27 (s, 1H), 7.24−7.16 (m,
3H), 6.31 (t, J = 2.0 Hz, 1H), 5.54 (s, 1H), 4.90 (s, 1H), 2.43 (s, 3H),
2.10 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.4, 144.0, 140.5,
136.6, 135.0, 130.5, 128.4, 127.4, 126.6, 126.0, 106.8, 104.1, 70.1, 20.8,
19.0; IR (neat) νmax 3128, 3024, 1745, 1232, 756 cm−1; MS (EI) m/z
(%) 257 (M+ + 1, 90), 229 (34), 215 (21), 197 (100), 182 (5). Anal.
Calcd for C15H16N2O2: C, 70.29; H, 6.29; N, 10.93. Found: C, 70.18;
H, 6.21; N, 10.85.
(E)-1,1′-(3-o-Tolylprop-1-ene-1,3-diyl)bis(1H-pyrazole) (5k): yel-
low oil (27 mg, 10% yield); Rf = 0.27 (4/1 hexane/EtOAc) [silica,
UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.61 (bd, J = 1.6 Hz, 1H),
7.60 (bd, J = 1.6 Hz, 1H), 7.51 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 2.0 Hz,
1H), 7.29−7.18 (m, 3H), 7.17−7.08 (m, 1H), 6.66−6.62 (m, 2H),
6.42 (d, J = 4.8 Hz, 1H), 6.34 (t, J = 2.4 Hz, 1H), 6.29 (t, J = 2.0 Hz,
1H), 2.29 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 141.3, 139.7,
136.5, 136.3, 130.9, 130.1, 128.6, 128.5, 128.4, 127.2, 126.5, 114.8,
107.3, 105.7, 61.9, 19.0; IR (neat) νmax 3024, 2924, 1678,1394, 960,
752 cm−1; MS (EI) m/z (%) 265 (M+ + 1, 100), 243 (4), 219 (12),
163 (12), 145 (8). Anal. Calcd for C16H16N4: C, 72.70; H, 6.10; N,
21.20. Found: C, 72.85; H, 6.04; N, 21.13.
(E)-1,1′-(3-(2-Bromophenyl)prop-2-ene-1,1-diyl)bis(1H-pyrazole)
(4l): pale yellow solid (165 mg, 50% yield); mp 74−75 °C; Rf = 0.33
(4/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 7.68 (bd, J = 2.4 Hz, 2H), 7.60 (bd, J = 1.6 Hz, 2H), 7.57
(dd, J = 8.0, 1.6 Hz, 1H), 7.51 (dd, J = 8.0, 1.2 Hz, 1H), 7.26 (d, J =
4.4 Hz, 1H), 7.23 (d, J = 6.0 Hz, 1H), 7.10 (td, J = 7.6, 1.6 Hz, 1H),
7.00−6.84 (m, 2H), 6.31 (t, J = 2.0 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ 140.4, 134.9, 134.2, 132.8, 129.8, 128.6, 127.4, 127.3, 125.3,
123.9, 106.6, 75.7; IR (KBr) νmax 3022, 2968, 1514, 1087, 968, 754
cm−1; MS (EI) m/z (%) 331 (M+ + 2, 78), 330 (M+ + 1, 100), 264
(11), 262 (11). Anal. Calcd for C15H13BrN4: C, 54.73; H, 3.98; N,
17.02. Found: C, 54.85; H, 3.91; N, 17.15.
1-(2-Bromophenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3l): pale
yellow semisolid (64 mg, 20% yield); Rf = 0.45 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J
= 2.4 Hz, 1H), 7.60 (bs, 1H), 7.58 (d, J = 1.2 Hz, 1H), 7.48 (dd, J =
6.8, 1.6 Hz, 1H), 7.35−7.29 (m, 2H), 7.21 (td, J = 6.8, 1.6 Hz, 1H),
6.33 (t, J = 2.0 Hz, 1H), 5.65 (bd, J = 1.2 Hz, 1H), 4.82 (bt, J = 1.2 Hz,
1H), 2.12 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.2, 142.8,
140.7, 136.1, 133.1, 130.1, 128.4, 127.6, 127.2, 123.9, 107.0, 104.6,
72.3, 20.7; IR (neat) νmax 3063, 2928, 1747, 1224, 756 cm−1; MS (EI)
m/z (%) 323 (M+ + 2, 28), 321 (M+, 28), 208 (17), 151 (100), 108
(34), 76 (38). Anal. Calcd for C14H13BrN2O2: C, 52.36; H, 4.08; N,
8.72. Found: C, 52.25; H, 4.12; N, 8.65.
1-(3-(tert-Butyldimethylsilyloxy)phenyl)-2-(1H-pyrazol-1-yl)allyl
acetate (3h): pale yellow oil (78 mg, 21% yield); Rf = 0.70 (4/1
1
hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ
7.58 (t, J = 2.4 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.06−6.99 (m, 2H),
6.88 (bt, J = 2.4 Hz, 1H), 6.77 (ddd, J = 8.4, 2.4, 0.8 Hz, 1H), 6.26 (t, J
= 2.4 Hz, 1H), 5.56 (bd, J = 0.8 Hz, 1H), 5.07 (s, 1H), 2.14 (s, 3H),
0.96 (s, 9H), 0.15 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 169.4,
155.7, 144.0, 140.6, 138.3, 129.5, 127.9, 120.3, 120.1, 119.0, 106.8,
103.5, 72.9, 25.6, 21.0, 18.2, −4.5; IR (neat) νmax 2957, 1751, 1602,
1226, 750 cm−1; MS (EI) m/z (%) 373 (M+ + 1, 100), 235 (9), 203
(9), 171 (3). Anal. Calcd for C20H28N2O3Si: C, 64.48; H, 7.58; N,
7.52. Found: C, 64.32; H, 7.63; N, 7.45.
(E)-1,1′-(3-(3-(tert-Butyldimethylsilyloxy)phenyl)prop-1-ene-1,3-
diyl)bis(1H-pyrazole) (5h): yellow oil (38 mg, 10% yield); Rf = 0.38
(4/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 7.61 (bd, J = 1.6 Hz, 1H), 7.60 (bd, J = 1.6 Hz, 1H), 7.54 (d,
J = 2.4 Hz, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H),
6.87−6.82 (m, 2H), 6.82−6.78 (m, 1H), 6.68−6.61 (m, 2H), 6.35 (t, J
= 2.0 Hz, 1H), 6.31 (t, J = 2.0 Hz, 1H), 6.15 (d, J = 6.8 Hz, 1H), 0.95
(s, 9H), 0.15 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 156.1, 141.3,
140.3, 139.7, 130.6, 129.8, 128.5, 128.3, 120.1, 119.9, 118.9, 114.7,
107.4, 105.8, 64.9, 25.6, 18.1, −4.5; IR (neat) νmax 2929, 1676, 1485,
1278, 748 cm−1; MS (EI) m/z (%) 381 (M+ + 1, 100), 201 (9), 145
(9), 105 (9). Anal. Calcd for C21H28N4OSi: C, 66.28; H, 7.42; N,
14.72. Found: C, 66.32; H, 7.51; N, 14.86.
(E)-1,1′-(3-(3-(Methoxymethoxy)phenyl)prop-2-ene-1,1-diyl)bis-
(1H-pyrazole) (4i): pale yallow solid (180 mg, 58% yield); mp 57−58
°C; Rf = 0.23 (4/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400
MHz, CDCl3) δ 7.66 (d, J = 2.4 Hz, 2H), 7.60 (bd, J = 1.6 Hz, 2H),
7.25 (t, J = 8.0 Hz, 1H), 7.17 (dd, J = 6.4, 1.6 Hz, 1H), 7.10 (bt, J = 2.4
Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.98 (ddd, J = 8.0, 2.4, 0.8 Hz, 1H),
6.91 (dd, J = 15.6, 6.0 Hz, 1H), 6.56 (dd, J = 16.0, 0.8 Hz, 1H), 6.32 (t,
J = 2.0 Hz, 2H), 5.17 (s, 2H), 3.47 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 157.4, 140.5, 136.5, 135.4, 129.6, 128.6, 123.0, 120.8, 116.7,
114.6, 106.6, 94.3, 76.1, 55.9; IR (KBr) νmax 2955, 1745, 1585, 1018,
756 cm−1; MS (EI) m/z (%) 311 (M+ + 1, 100), 269 (6), 227 (3).
Anal. Calcd for C17H18N4O2: C, 65.79; H, 5.85; N, 18.05. Found: C,
65.58; H, 5.76; N, 18.21.
1-(3-(Methoxymethoxy)phenyl)-2-(1H-pyrazol-1-yl)allyl acetate
(3i): yellow oil (63 mg, 21% yield); Rf = 0.41 (4/1 hexane/EtOAc)
1
[silica, UV and I2]; H NMR (400 MHz, CDCl3) δ 7.59 (bd, J = 2.4
Hz, 1H), 7.58 (bd, J = 1.6 Hz, 1H), 7.28−7.20 (m, 1H), 7.08 (bt, J =
2.0 Hz, 1H), 7.07−7.03 (m, 2H), 6.98 (ddd, J = 8.4, 2.4, 1.2 Hz, 1H),
6.26 (t, J = 2.0 Hz, 1H), 5.56 (bd, J = 1.2 Hz, 1H), 5.13 (s, 2H), 5.09
(s, 1H), 3.45 (s, 3H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
11831
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The Journal of Organic Chemistry
Article
(E)-1,1′-(3-(2,4-Dichlorophenyl)prop-2-ene-1,1-diyl)bis(1H-pyra-
zole) (4m): colorless solid (210 mg, 66% yield); mp =107−108 °C; Rf
= 0.54 (6/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 7.65 (d, J = 2.4 Hz, 2H), 7.60 (bd, J = 1.6 Hz, 2H), 7.50 (dd,
J = 8.4, 2.8 Hz, 1H), 7.33 (bt, J = 2.4 Hz, 1H), 7.22 (d, J = 3.2 Hz,
1H), 7.18 (dt, J = 8.4, 2.4 Hz, 1H), 6.94−6.91 (m, 2H), 6.31 (bt, J =
2.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 140.5, 134.7, 134.0,
131.8, 130.5, 129.4, 128.6, 127.9, 127.2, 125.8, 106.7, 75.8; IR (KBr)
νmax 3109, 2962, 1585, 1388, 754 cm−1; MS (EI) m/z (%) 320 (M+ +
1, 8), 290 (13), 251 (100), 215 (21), 183 (11), 102 (8). Anal. Calcd
for C15H12Cl2N4: C, 56.44; H, 3.79; N, 17.55. Found: C, 56.32; H,
3.83; N, 17.41.
(E)-1,1′-(3-(Naphthalen-1-yl)prop-1-ene-1,3-diyl)bis(1H-pyrazole)
(5o): pale yellow solid (48 mg, 16% yield); mp 95−96 °C; Rf = 0.29
(4/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 8.00−7.93 (m, 1H), 7.92−7.83 (m, 2H), 7.63 (d, J = 12.8
Hz, 2H), 7.53−7.41 (m, 5H), 7.33 (bd, J = 2.0 Hz, 1H), 7.02 (d, J =
5.6 Hz, 1H), 6.82 (dd, J = 14.0, 6.0 Hz, 1H), 6.63 (d, J = 14.0 Hz, 1H),
6.32 (bt, J = 2.0 Hz, 1H), 6.26 (bt, J = 2.0 Hz, 1H); 13C NMR (101
MHz, CDCl3) δ 141.3, 139.7, 133.9, 133.8, 130.9, 130.2, 129.5, 128.84,
128.77, 128.5, 126.9, 126.0, 125.7, 125.2, 122.9, 115.0, 107.2, 105.9,
61.7; IR (KBr) νmax 3051, 2924, 1678, 1394, 958, 754 cm−1; MS (EI)
m/z (%) 301 (M+ + 1, 100), 282 (11). Anal. Calcd for C19H16N4: C,
75.98; H, 5.37; N, 18.65. Found: C, 75.85; H, 5.32; N, 18.71.
1-(2,4-Dichlorophenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3m): pale
(E)-1,1′-(3-(Thiophen-2-yl)prop-2-ene-1,1-diyl)bis(1H-pyrazole)
yellow solid (47 mg, 15% yield); mp 57−58 °C; Rf = 0.57 (6/1
(4p): brown solid (141 mg, 55% yield); mp 63−64 °C; Rf = 0.35 (6/1
1
1
hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ
hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz, CDCl3) δ
7.68 (d, J = 2.4 Hz, 1H), 7.58 (bd, J = 1.6 Hz, 1H), 7.41 (d, J = 11.2
Hz, 1H), 7.42 (s, 1H), 7.34 (s, 1H), 7.25 (dd, J = 8.4, 2.0 Hz, 1H),
6.32 (bt, J = 2.0 Hz, 1H), 5.60 (bd, J = 1.6 Hz, 1H), 4.88 (bt, J = 1.2
Hz, 1H), 2.12 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.1, 142.6,
140.8, 135.1, 134.6, 133.3, 129.7, 129.3, 127.34, 127.28, 107.2, 104.2,
69.6, 20.7; IR (KBr) νmax 3128, 2932, 1751, 1222, 1026, 754 cm−1; MS
(EI) m/z (%) 313 (M+ + 2, 67), 311 (M+, 100), 289 (41), 253 (41),
251 (61), 216 (14), 102 (14). Anal. Calcd for C14H12Cl2N2O2: C,
54.04; H, 3.89; N, 9.00. Found: C, 54.15; H, 3.81; N, 8.86.
7.64 (bd, J = 2.4 Hz, 2H), 7.59 (bd, J = 1.6 Hz, 2H), 7.18 (dd, J = 11.2,
4.8 Hz, 2H), 6.99 (d, J = 3.6 Hz, 1H), 6.93 (t, J = 4.4 Hz, 1H), 6.69 (d,
J = 5.2 Hz, 1H), 6.67 (s, 1H), 6.29 (bt, J = 2.4 Hz, 2H); 13C NMR
(101 MHz, CDCl3) δ 140.3, 139.6, 128.5, 128.4, 127.7, 127.3, 125.8,
121.4, 106.5, 75.6; IR (KBr) νmax 3107, 1649, 1514, 1390, 1087, 960,
754 cm−1; MS (EI) m/z (%) 257 (M+ + 1, 100), 243 (3), 211 (30),
167 (16), 97 (6). Anal. Calcd for C13H12N4S: C, 60.91; H, 4.72; N,
21.86. Found: C, 60.75; H, 4.81; N, 21.75.
2-(1H-Pyrazol-1-yl)-1-(thiophen-2-yl)allyl acetate (3p): brown oil
(30 mg, 12% yield); Rf = 0.56 (6/1 hexane/EtOAc) [silica, UV and
I2]; 1H NMR (400 MHz, CDCl3) δ 7.66 (bd, J = 2.0 Hz, 1H), 7.61 (s,
1H), 7.34 (s, 1H), 7.27 (bd, J = 3.2 Hz, 1H), 7.09 (bd, J = 3.2 Hz, 1H),
6.93 (t, J = 4.0 Hz, 1H), 6.31 (bs, 1H), 5.57 (s, 1H), 5.27 (s, 1H), 2.15
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.2, 143.8, 140.7, 139.9,
128.0, 127.3, 126.8, 126.3, 107.0, 102.9, 68.8, 21.0; IR (neat) νmax
2926, 1747, 1653, 1224, 1024, 754 cm−1; MS (EI) m/z (%) 247 (M+−
1, 100), 244 (54), 220 (30), 186 (6), 136 (3). Anal. Calcd for
C12H12N2O2S: C, 58.05; H, 4.87; N, 11.28. Found: C, 58.12; H, 4.81;
N, 11.35.
(E)-1,1′-(3-(2,6-Dichlorophenyl)prop-2-ene-1,1-diyl)bis(1H-pyra-
zole) (4n): colorless solid (162 mg, 51% yield); mp 105−106 °C; Rf =
1
0.64 (4/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400 MHz,
CDCl3) δ 7.73 (s, 2H), 7.60 (s, 2H), 7.33−7.25 (m, 3H), 7.10 (t, J =
7.6 Hz, 1H), 6.96 (dd, J = 16.4, 4.4 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H),
6.32 (bd, J = 1.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 140.6,
134.4, 132.5, 131.2, 129.4, 129.0, 128.8, 128.4, 106.6, 75.8; IR (KBr)
νmax 3109, 2962, 1582, 1388, 1041, 754 cm−1; MS (EI) m/z (%) 320
(M+ + 1, 37), 319 (M+, 100), 146 (4), 110 (4). Anal. Calcd for
C15H12Cl2N4: C, 56.44; H, 3.79; N, 17.55. Found: C, 56.51; H, 3.72;
N, 17.41.
1-(2,6-Dichlorophenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3n): col-
orless solid (37 mg, 12% yield); mp 86−87 °C; Rf = 0.57 (6/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.83 (bdd,
J = 8.4, 1.6 Hz, 1H), 7.65 (bs, 1H), 7.60 (bd, J = 2.0 Hz, 1H), 7.30 (s,
1H), 7.28 (s, 1H), 7.13 (t, J = 8.0 Hz, 1H), 6.88 (d, J = 9.6 Hz, 1H),
6.34 (bt, J = 2.0 Hz, 1H), 5.74 (t, J = 8.8 Hz, 1H), 2.09 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 170.0, 141.6, 135.4, 134.7, 130.5, 129.5,
129.2, 128.0, 113.3, 106.9, 68.8, 20.9; IR (KBr) νmax 2924, 1730, 1244,
761 cm−1; MS (EI) m/z (%) 313 (M+ + 2, 20), 311 (M+, 35), 289
(17), 251 (100), 203 (100), 183 (41), 130 (17), 102 (100). Anal.
Calcd for C14H12Cl2N2O2: C, 54.04; H, 3.89; N, 9.00. Found: C,
53.95; H, 3.94; N, 9.12.
(E)-1,1′-(3-(Thiophen-2-yl)prop-1-ene-1,3-diyl)bis(1H-pyrazole)
(5p): brown oil (18 mg, 7% yield); Rf = 0.20 (6/1 hexane/EtOAc)
1
[silica, UV and I2]; H NMR (400 MHz, CDCl3) δ 7.62 (bd, J = 1.6
Hz, 1H), 7.60 (bd, J = 1.6 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.50 (d, J
= 2.4 Hz, 1H), 7.32 (dd, J = 5.2, 1.2 Hz, 1H), 7.06 (bd, J = 3.6 Hz,
1H), 7.01 (dd, J = 5.2, 3.6 Hz, 1H), 6.92 (d, J = 13.6 Hz, 1H), 6.67
(dd, J = 14.0, 6.8 Hz, 1H), 6.43 (d, J = 7.2 Hz, 1H), 6.36 (bt, J = 2.0
Hz, 1H), 6.31 (bt, J = 2.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ
141.7, 141.5, 139.8, 130.3, 128.5, 128.1, 127.0, 126.5, 126.3, 114.7,
107.5, 106.1, 60.7; IR (neat) νmax 3107, 2924, 1678, 1520, 1394, 1089,
752 cm−1; MS (EI) m/z (%) 257 (M+ + 1, 100), 239 (6), 215 (6), 181
(9), 157 (12), 133 (12). Anal. Calcd for C13H12N4S: C, 60.91; H, 4.72;
N, 21.86. Found: C, 61.06; H, 4.68; N, 21.95.
(E)-1,1′-(3-(Naphthalen-1-yl)prop-2-ene-1,1-diyl)bis(1H-pyrazole)
(4o): colorless solid (144 mg, 48% yield); mp 85−86 °C; Rf = 0.38 (4/
1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ
8.01−7.94 (m, 1H), 7.89−7.81 (m, 2H), 7.75 (bd, J = 2.4 Hz, 2H),
7.72−7.65 (m, 3H), 7.54−7.44 (m, 3H), 7.35 (dd, J = 10.4, 4.4 Hz,
2H), 6.97 (dd, J = 16.0, 5.6 Hz, 1H), 6.37 (bt, J = 2.0 Hz, 2H); 13C
NMR (101 MHz, CDCl3) δ 140.5, 133.4, 132.9, 132.6, 130.9, 129.0,
128.6, 128.5, 126.3, 125.9, 125.6, 125.4, 124.4, 123.3, 106.7, 76.1; IR
(KBr) νmax 3117, 3057, 1512, 1390, 966, 754 cm−1; MS (EI) m/z (%)
301 (M+ + 1, 100), 287 (6), 255 (4). Anal. Calcd for C19H16N4: C,
75.98; H, 5.37; N, 18.65. Found: C, 75.86; H, 5.31; N, 18.56.
1-(Naphthalen-1-yl)-2-(1H-pyrazol-1-yl)allyl acetate (3o): color-
less solid (67 mg, 23% yield); mp 92−93 °C; Rf = 0.56 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J
= 8.4 Hz, 1H), 7.93 (s, 1H), 7.87 (dd, J = 11.6, 8.4 Hz, 2H), 7.71−7.64
(m, 2H), 7.62 (bd, J = 1.6 Hz, 1H), 7.59−7.49 (m, 2H), 6.47 (t, J = 7.6
Hz,. 1H), 6.31 (bt, J = 1.6 Hz,. 1H), 5.62 (bd, J = 1.2 Hz, 1H), 4.95 (s,
1H), 2.14 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.5, 143.9,
140.7, 133.7, 132.4, 130.9, 129.4, 128.7, 127.4, 126.7, 125.9, 125.1,
123.4, 107.0, 104.6, 70.0, 20.9; IR (KBr) νmax 3065, 2930, 1736, 1224,
773 cm−1; MS (EI) m/z (%) 293 (M+ + 1, 100). Anal. Calcd for
C18H16N2O2: C, 73.95; H, 5.52; N, 9.58. Found: C, 74.05; H, 5.48; N,
9.51.
(E)-4-(3,3-Bis(1H-pyrazol-1-yl)prop-1-enyl)benzaldehyde (4q):
pale yellow solid (150 mg, 54% yield); mp 104−105 °C; Rf = 0.29
(3/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 9.99 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 2.4 Hz,
2H), 7.61 (bd, J = 1.6 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.21 (dd, J =
5.6, 1.2 Hz, 1H), 7.06 (dd, J = 16.0, 6.0 Hz, 1H), 6.61 (d, J = 16.0 Hz,
1H), 6.34 (bd, J = 2.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 191.4,
140.7, 140.5, 136.0, 134.0, 129.9, 128.6, 127.4, 126.1, 106.8, 75.7; IR
(KBr) νmax 2926, 1691, 1390, 1209, 1089, 765, 625 cm−1; MS (EI) m/
z (%) 279 (M+ + 1, 100), 233 (3), 212 (5). Anal. Calcd for
C16H14N4O: C, 69.05; H, 5.07; N, 20.13. Found: C, 69.18; H, 5.15; N,
20.06.
1-(4-Formylphenyl)-2-(1H-pyrazol-1-yl)allyl acetate (3q): pale
yellow oil (51 mg, 19% yield); Rf = 0.61 (3/1 hexane/EtOAc) [silica,
UV and I2]; 1H NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 7.82 (d, J =
8.0 Hz, 2H), 7.63−7.55 (m, 4H), 7.17 (s, 1H), 6.26 (bt, J = 2.0 Hz,
1H), 5.51 (bd, J = 1.2 Hz, 1H), 5.12 (s, 1H), 2.15 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 191.6, 169.1, 143.6, 140.7, 136.2, 129.8, 127.8,
127.7, 107.1, 103.1, 72.5, 20.9; IR (neat) νmax 2928, 1741, 1608, 1226,
1032, 758 cm−1; MS (EI) m/z (%) 271 (M+ + 1, 100), 240 (5). Anal.
Calcd for C15H14N2O3: C, 66.66; H, 5.22; N, 10.36. Found: C, 66.48;
H, 5.32; N, 10.25.
11832
dx.doi.org/10.1021/jo401867e | J. Org. Chem. 2013, 78, 11824−11834

The Journal of Organic Chemistry
Article
(E)-1,1′-(3-(4-(1,3-Dioxan-2-yl)phenyl)prop-2-ene-1,1-diyl)bis(1H-
pyrazole) (4r): colorless solid (145 mg, 43% yield); mp 120−121 °C;
147.6, 141.3, 139.7, 132.6, 130.4, 128.4, 128.3, 120.9, 115.0, 108.4,
107.8, 107.4, 105.8, 101.3, 64.8; IR (neat) νmax 2924, 1678, 1248, 1039,
754 cm−1; MS (EI) m/z (%) 295 (M+ + 1, 100), 252 (41), 204 (14).
Anal. Calcd for C16H14N4O2: C, 65.30; H, 4.79; N, 19.04. Found: C,
65.48; H, 4.85; N, 18.89.
1
Rf = 0.25 (3/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400
MHz, CDCl3) δ 7.65 (bd, J = 1.6 Hz, 2H), 7.59 (bs, 2H), 7.46 (bd, J =
6.8 Hz, 2H), 7.41 (bd, J = 6.4 Hz, 2H), 7.20 (dd, J = 5.2, 1.2 Hz, 1H),
6.91 (dd, J = 12.8, 4.8 Hz, 1H), 6.56 (d, J = 12.8 Hz, 1H), 6.29 (bd, J =
1.6 Hz, 2H), 5.47 (s, 1H), 4.23 (bdd, J = 8.8, 3.6 Hz, 2H), 3.94 (t, J =
10.0 Hz, 2H), 2.25−2.12 (m, 1H), 1.40 (bd, J = 10.0 Hz, 1H); 13C
NMR (101 MHz, CDCl3) δ 140.2, 139.0, 135.2, 135.0, 128.5, 126.7,
126.1, 122.7, 106.4, 100.8, 75.8, 67.0, 25.4; IR (KBr) νmax 3101, 2962,
1392, 1105, 758 cm−1; MS (EI) m/z (%) 337 (M+ + 1, 100), 323 (3).
Anal. Calcd for C19H20N4O2: C, 67.84; H, 5.99; N, 16.66. Found: C,
67.71; H, 5.91; N, 16.58.
1-(4-(1,3-Dioxan-2-yl)phenyl)-2-(1H-pyrazol-1-yl)allyl acetate
(3r): colorless solid (66 mg, 20% yield); mp 119−120 °C; Rf = 0.44
(3/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400 MHz,
CDCl3) δ 7.56 (bt, J = 2.0 Hz, 2H), 7.49−7.42 (m, 4H), 7.11 (s, 1H),
6.24 (t, J = 2.0 Hz, 1H), 5.56 (s, 1H), 5.48 (s, 1H), 5.09 (s, 1H), 4.25
(dd, J = 8.8, 4.0 Hz, 2H), 3.97 (td, J = 9.6, 1.6 Hz, 2H), 2.26−2.16 (m,
1H), 2.12 (s, 3H), 1.44 (d, J = 10.8 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 169.2, 143.9, 140.5, 138.9, 137.4, 127.8, 127.2, 126.2, 106.8,
103.3, 101.0, 72.8, 67.3, 25.6, 20.9; IR (KBr) νmax 3130, 2974, 1738,
1244, 763 cm−1; MS (EI) m/z (%) 329 (M+ + 1, 100), 223 (11), 121
(3). Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found:
C, 65.72; H, 6.21; N, 8.65.
1-Phenyl-3-(1H-pyrazol-1-yl)but-3-en-2-yl acetate (3t): colorless
oil (49 mg, 19% yield); Rf = 0.57 (19/1 hexane/EtOAc) [silica, UV
1
and I2]; H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.67 (s, 1H),
7.48−7.12 (m, 5H), 6.38 (s, 1H), 6.22 (s, 1H), 5.33 (s, 1H), 4.95 (s,
1H), 3.23−3.13 (m, 1H), 3.06−2.90 (m, 1H), 2.06 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 169.6, 144.2, 140.8, 136.7, 129.5, 128.2, 127.8,
126.7, 107.0, 102.3, 39.6, 21.0; IR (neat) νmax 3030, 2926, 1747, 1651,
1232, 1045, 754 cm−1; MS (EI) m/z (%) 257 (M+ + 1, 100), 199 (8),
167 (14), 139 (5). Anal. Calcd for C15H16N2O2: C, 70.29; H, 6.29; N,
10.93. Found: C, 70.18; H, 6.22; N, 10.88.
(Z)-1-Phenyl-4-(1H-pyrazol-1-yl)but-3-en-2-yl acetate (3t′). color-
less oil (65 mg, 25% yield); Rf = 0.45 (19/1 hexane/EtOAc) [silica,
UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.50 (s, 1H),
7.36−7.18 (m, 5H), 6.74 (d, J = 9.6 Hz, 1H), 6.56 (s, 1H), 6.34 (s,
1H), 5.14 (t, J = 8.8 Hz, 1H), 3.24−3.15 (m, 1H), 3.05−2.98 (m, 1H),
1.99 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 170.1, 141.4, 137.2,
130.3, 129.6, 128.1, 126.4, 125.7, 117.2, 106.6, 71.5, 40.4, 21.1; IR
(neat) νmax 3028, 2924, 1736, 1521, 1236, 738 cm−1; MS (EI) m/z
(%) 257 (M+ + 1, 100), 223 (14), 211 (27), 167 (14), 97 (11), 91
(11). Anal. Calcd for C15H16N2O2: C, 70.29; H, 6.29; N, 10.93. Found:
C, 70.35; H, 6.23; N, 10.99.
1-(Naphthalen-1-yl)-2-(1H-pyrazol-1-yl)propan-1-ol (7): pale yel-
low oil (45 mg, 89% yield); Rf = 0.61 (4/1 hexane/EtOAc) [silica, UV
and I2]; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 2H), 7.87
(d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.59 (bd, J = 1.6 Hz,
2H), 7.57−7.47 (m, 4H), 7.32 (t, J = 8.0 Hz, 2H), 7.13−7.06 (m, 4H),
6.12 (t, J = 2.4 Hz, 2H), 4.77−4.67 (m, 2H), 3.70 (dd, J = 14.0, 7.2 Hz,
2H), 3.46 (dd, J = 13.6, 6.8 Hz, 2H), 1.62 (s, 3H), 1.61 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 139.1, 134.0, 133.8, 131.8, 128.8, 127.8,
127.5, 127.4, 126.1, 125.5, 125.3, 123.4, 104.5, 58.6, 40.9, 20.6; IR
(neat) νmax 3059, 2934, 1745, 1396, 1045, 750, 623 cm−1; MS (EI) m/
z (%) 253 (M+ + 1, 100), 207 (3), 184 (3), 168 (3). Anal. Calcd for
C16H16N2O: C, 76.16; H, 6.39; N, 11.10. Found: C, 76.28; H, 6.31; N,
11.25.
(E)-1,1′-(3-(4-(1,3-Dioxan-2-yl)phenyl)prop-1-ene-1,3-diyl)bis(1H-
pyrazole) (5r): pale yellow solid (47 mg, 14% yield); mp 105−106 °C;
1
Rf = 0.17 (3/1 hexane/EtOAc) [silica, UV and I2]; H NMR (400
MHz, CDCl3) δ 7.61 (bd, J = 1.2 Hz, 1H), 7.59 (bd, J = 1.2 Hz, 1H),
7.53−7.48 (m, 3H), 7.43 (d, J = 1.6 Hz, 1H), 7.25 (d, J = 6.4 Hz, 2H),
6.77 (dd, J = 11.2, 0.4 Hz, 1H), 6.68 (dd, J = 11.2, 5.2 Hz, 1H), 6.34
(bt, J = 2.0 Hz, 1H), 6.29 (bt, J = 1.6 Hz, 1H), 6.23 (d, J = 5.6 Hz,
1H), 5.51 (s, 1H), 4.26 (dd, J = 8.4, 3.6 Hz, 2H), 3.99 (td, J = 10.0, 2.0
Hz, 2H), 2.28−2.16 (m, 1H), 1.45 (d, J = 10.8 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 141.3, 139.6, 139.1, 138.9, 130.5, 128.5, 128.4,
127.2, 126.5, 114.8, 107.3, 105.8, 100.9, 67.3, 64.8, 25.6; IR (KBr) νmax
3111, 2924, 1676, 1392, 1103, 748 cm−1; MS (EI) m/z (%) 337 (M+ +
1, 100), 323 (3). Anal. Calcd for C19H20N4O2: C, 67.84; H, 5.99; N,
16.66. Found: C, 67.92; H, 6.08; N, 16.75.
(E)-1,1′-(3-(Benzo[d][1,3]dioxol-5-yl)prop-2-ene-1,1-diyl)bis(1H-
pyrazole) (4s): light brown solid (147 mg, 50% yield); mp 115−116
°C; Rf = 0.43 (6/1 hexane/EtOAc) [silica, UV and I2]; 1H NMR (400
MHz, CDCl3) δ 7.64 (bd, J = 2.0 Hz, 2H), 7.59 (bd, J = 1.6 Hz, 2H),
7.13 (d, J = 6.0 Hz, 1H), 6.98 (bd, J = 1.2 Hz, 1H), 6.84 (d, J = 8.0 Hz,
1H), 6.78−6.70 (m, 2H), 6.50 (d, J = 16.0 Hz, 1H), 6.31 (bt, J = 2.0
Hz, 2H), 5.95 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 148.2, 148.1,
140.4, 135.3, 129.5, 128.5, 122.3, 120.7, 108.3, 106.6, 106.1, 101.2,
76.3; IR (KBr) νmax 3103, 2901, 1651, 1448, 1255, 1037, 761, 625
cm−1; MS (EI) m/z (%) 294 (M+, 24), 293 (M+−1, 100). Anal. Calcd
for C16H14N4O2: C, 65.30; H, 4.79; N, 19.04. Found: C, 65.21; H,
4.71; N, 19.15.
1-(Benzo[d][1,3]dioxol-5-yl)-2-(1H-pyrazol-1-yl)allyl acetate (3s):
brown oil (29 mg, 10% yield); Rf = 0.64 (6/1 hexane/EtOAc) [silica,
UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.58 (bd, J = 2.8 Hz, 1H),
7.57 (bd, J = 1.6 Hz, 1H), 6.99 (s, 1H), 6.96−6.90 (m, 2H), 6.73 (d, J
= 8.4 Hz, 1H), 6.26 (bt, J = 2.0 Hz, 1H), 5.92 (s, 2H), 5.53 (s, 1H),
5.12 (s, 1H), 2.12 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.3, 147,
77, 147.76, 144.1, 140.5, 130.6, 127.7, 121.4, 108.2, 107.8, 106.8, 102.8,
101.2, 72.8, 21.0; IR (neat) νmax 2924, 1743, 1228, 756, 696 cm−1; MS
(EI) m/z (%) 287 (M+ + 1, 100), 269 (6), 241 (9), 229 (14), 197 (8).
Anal. Calcd for C15H14N2O4: C, 62.93; H, 4.93; N, 9.79. Found: C,
62.85; H, 4.88; N, 9.65.
1,1′-(3-Phenylpropane-1,1-diyl)bis(1H-pyrazole) (8): colorless
solid (99 mg, 98% yield); mp 69−70 °C; Rf = 0.35 (4/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.63 (bd, J
= 2.4 Hz, 2H), 7.56 (bd, J = 1.6 Hz, 2H), 7.31 (bt, J = 7.6 Hz, 2H),
7.26−7.19 (m, 1H), 7.15 (bd, J = 1.6 Hz, 1H), 7.14 (s, 1H), 6.33 (t, J
= 7.6 Hz, 1H), 6.28 (bt, J = 2.0 Hz, 2H), 2.95 (q, J = 7.2 Hz, 2H), 2.58
(t, J = 7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 140.0, 139.6,
128.6, 128.5, 128.4, 126.4, 106.4, 74.5, 35.1, 31.1. IR (KBr) νmax 3109,
2928, 1514, 1390, 1091, 752, 623 cm−1; MS (EI) m/z (%) 253 (M+ +
1, 100), 209 (3), 146 (3). Anal. Calcd for C15H16N4: C, 71.40; H, 6.39;
N, 22.21. Found: C, 71.56; H, 6.31; N, 22.15.
Synthesis of Pd Complex 9 from 4o: pale yellow solid (127 mg,
1
89% yield); mp 275−276 °C dec; H NMR (400 MHz, DMSO-d6) δ
8.46 (bd, J = 2.4 Hz, 2H), 8.25 (bd, J = 4.0 Hz, 1H), 8.22 (d, J = 8.8
Hz, 1H), 8.08 (bd, J = 1.2 Hz, 2H), 8.03−7.89 (m, 3H), 7.67−7.45
(m, 4H), 7.10 (bs, 1H), 6.68 (s, 2H); 13C NMR (101 MHz, DMSO-
d6) δ 144.4, 135.3, 133.6, 132.1, 131.1, 130.0, 129.0, 127.3, 126.7,
126.2, 125.3, 124.2, 108.1, 73.8; IR (KBr) νmax 3145, 3123, 2931, 1408,
1282, 1205, 1086, 947, 860, 783, 613 cm−1. Anal. Calcd for
C19H16Cl2N4Pd: C, 47.77; H, 3.38; N, 11.73. Found: C, 47.86; H,
3.32; N, 11.65.
Synthesis of Pd Complex 10 from 8: pale yellow solid (150 mg,
88% yield); mp 254−256 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.23
(s, 2H), 8.00 (s, 2H), 7.36−7.26 (m, 3H), 7.24−7.16 (m, 4H), 6.58 (s,
1H), 3.52 (bs, 2H), 2.35 (bs, 2H); 13C NMR (101 MHz, DMSO-d6) δ
144.3, 139.3, 135.5, 129.1, 128.6, 126.9, 107.7, 73.3, 39.3 (merged in
DMSO-d6 peaks), 30.6; IR (KBr) νmax 3139, 3123, 3013, 2969, 2926,
1408, 1298, 1216, 1068, 772, 756, 695 cm−1; HRMS calcd for
C15H16Cl2N4Pd [M + Na]+ 450.9685, found 450.9685.
(E)-1,1′-(3-(Benzo[d][1,3]dioxol-5-yl)prop-1-ene-1,3-diyl)bis(1H-
pyrazole) (5s): brown oil (50 mg, 17% yield); Rf = 0.18 (6/1 hexane/
EtOAc) [silica, UV and I2]; 1H NMR (400 MHz, CDCl3) δ 7.62 (bd, J
= 1.6 Hz, 1H), 7.60 (bd, J = 1.2 Hz, 1H), 7.56 (bd, J = 2.0 Hz, 1H),
7.48 (bd, J = 2.0 Hz, 1H), 6.83 (d, J = 11.6 Hz, 1H), 6.81−6.75 (m,
2H), 6.74 (bd, J = 1.2 Hz, 1H), 6.64 (dd, J = 11.2, 5.6 Hz, 1H), 6.36
(bt, J = 1.6 Hz, 1H), 6.31 (bt, J = 1.6 Hz, 1H), 6.12 (d, J = 5.6 Hz,
1H), 5.97−5.95 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 148.1,
General Procedure for Suzuki−Miyaura Cross Coupling
Reaction GP-4. A 25 mL Schlenk tube was charged with aryl halides
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dx.doi.org/10.1021/jo401867e | J. Org. Chem. 2013, 78, 11824−11834

The Journal of Organic Chemistry
Article
(11; 1.0 equiv), arylboronic acids (12; 2.0 equiv), K2CO3 (2.0 equiv),
and palladium complex 9/10 (0.1 mol %) in H2O. The reaction
mixture was stirred at 80 °C for 24 h. After the mixture was cooled to
room temperature, it was diluted with water and extracted with EtOAc.
The organic layer was separated, dried over Na2SO4, and concentrated
under vacuum. The crude residue was purified using column
chromatography on silica gel. Analytical and spectral data of cross-
coupled products 13 exactly match with the reported values. 4-
Methoxybiphenyl (13aa):16 536 mg, 97% yield. 4-(Trifluoromethyl)-
biphenyl (13ba):17 480 mg, 72% yield. 2-Methylbiphenyl (13ca):18
473 mg, 94% yield. 2-Phenylthiophene (13da):16 385 mg, 80% yield.
4-Fluoro-4′-methoxybiphenyl (13ab):19 577 mg, 95% yield. 4′-
Methoxy-3-methylbiphenyl (13ac):17 511 mg, 86% yield. 1-(4-
Methoxyphenyl)naphthalene (13ad):20 674 mg, 96% yield.
(4) Pavlov, P. T.; Goleneva, A. F.; Lesnov, A. E.; Prokhorova, T. S.
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chez, A. Dalton Trans. 2004, 1499.
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reverse trend of product selectivity was observed when O-Boc-
protected propargyl alcohols reacted with pyrazole; 3 (16%), 4 (21%),
and 5 (52%).
(9) Kumar, M. P.; Liu, R.-S. J. Org. Chem. 2006, 71, 4951.
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Organic Synthesis, 4th ed.; Wiley: New York, 2007.
(11) See the Supporting Information.
(12) Hashmi, A. S. K.; Rudolph, M.; Bats, J. W.; Frey, W.; Rominger,
F.; Oeser, T. Chem. Eur. J. 2008, 14, 6672.
(13) (a) Regina, G. L.; D’Auria, F. D.; Tafi, A.; Piscitelli, F.; Olla, S.;
Caporuscio, F.; Nencioni, L.; Cirilli, R.; Torre, F. L.; De Melo, N. R.;
Kelly, S. L.; Lamb, D. C.; Artico, M.; Botta, M.; Palamara, A. T.;
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Figures giving H and 13C NMR spectra of new compounds
and tables and CIF files giving crystallographic details of
compounds 4n, 3o, 5o, and 9. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for A.K.S.: akssc@uohyd.ernet.in and
akhilchemistry12@gmail.com.
■
Notes
The authors declare no competing financial interest.
Silvestri, R. J. Med. Chem. 2008, 51, 3841. (b) Bosak, A.; Smilovic,
́
I.
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G.; Sinko, G.; Vinkovic,
(14) (a) Naj
Lett. 2003, 5, 1451. (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis
2004, 2419. (c) Franzen, R.; Xu, Y. Can. J. Chem. 2005, 83, 266.
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V.; Kovarik, Z. J. Med. Chem. 2012, 55, 6716.
ACKNOWLEDGMENTS
■
́
era, C.; Gil-Molto, J.; Karlstrom, S.; Falvello, L. R. Org.
́
̈
We thank the UoH and ACRHEM for financial support. M.B.
and M.R.K. thank the CSIR of India, for fellowships. We are
grateful to Ms. Priyanka, Mr. Prabagar B, and the support of the
UGC-NWC. Dedicated to Professor M. Periasamy, University
of Hyderabad, India, on the occasion of his 60th birthday.
́
(d) Liu, C.; Ni, Q.; Hu, P.; Qiu, J. Org. Biomol. Chem. 2011, 9, 1054.
(e) Luo, Q.-L.; Tan, J.-P.; Li, Z.-F.; Nan, W.-H.; Xiao, D.-R. J. Org.
Chem. 2012, 77, 8332. (f) Mondal, M.; Bora, U. Green Chem. 2012, 14,
1873. (g) Wan, J.-P.; Wang, C.; Zhoua, R.; Liu, Y. RSC Advances 2012,
2, 8789. (h) Enderlin, G.; Sartori, G.; Herve, G.; Len, C. Tetrahedron
Lett. 2013, 54, 3374.
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