3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles: Synthesis and diels - Alder transformations

Article abstract of DOI:10.1002/ejoc.200400407

Reactions between cinnamoyl(2-hydroxybenzoyl)methanes and hydrazine hydrate in acetic acid gave 3-(2-hydroxyphenyl)-5-styrylpyrazoles, while the corresponding reactions with phenylhydrazine yielded 5-(2-hydroxyphenyl)-l- phenyl-3-styrylpyrazoles as the major products and 3-(2-hydroxyphenyl)-1-phenyl- 5-styrylpyrazoles as by-products. The reaction mechanism of this transformation is discussed. The first cycloaddition reactions between ortho- benzoquinodimethane and either 3-(2-hydroxyphenyl)-5-styrylpyrazoles or 5-(2-hydroxyphenyl)-1-phenyl-3-styrylpyrazoles afforded 5-[2-(3 aryl-1,2,3,4-tetrahydronaphthyl)]-3-(2-hydroxyphenyl)-pyrazoles or 3-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-1-phenyl-5-(2-hydroxyphenyl)pyrazoles, respectively. These cycloadducts were converted into the corresponding naphthylpyrazoles by oxidation with DDQ in dry 1,4-dioxane. The structures of all new derivatives have been established by NMR spectroscopy. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400407

FULL PAPER
3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles: Synthesis and Diels؊Alder
Transformations
[a]
[a]
[a]
[a]
´
Vera L. M. Silva, Artur M. S. Silva,* Diana C. G. A. Pinto, Jose A. S. Cavaleiro, and
[b]
´
Jose Elguero
Keywords: ortho-Benzoquinodimethane / DDQ / Dehydrogenation reactions / DielsϪAlder reactions / NMR
spectroscopy / Pyrazoles
Reactions between cinnamoyl(2-hydroxybenzoyl)methanes
aryl-1,2,3,4-tetrahydronaphthyl)]-3-(2-hydroxyphenyl)-
and hydrazine hydrate in acetic acid gave 3-(2-hydroxyphen- pyrazoles or 3-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-1-
yl)-5-styrylpyrazoles, while the corresponding reactions with
phenylhydrazine yielded 5-(2-hydroxyphenyl)-1-phenyl-3-
phenyl-5-(2-hydroxyphenyl)pyrazoles, respectively. These
cycloadducts were converted into the corresponding naph-
styrylpyrazoles as the major products and 3-(2-hydroxyphe- thylpyrazoles by oxidation with DDQ in dry 1,4-dioxane. The
nyl)-1-phenyl-5-styrylpyrazoles as by-products. The reaction structures of all new derivatives have been established by
mechanism of this transformation is discussed. The first cyc- NMR spectroscopy.
loaddition reactions between ortho-benzoquinodimethane
and either 3-(2-hydroxyphenyl)-5-styrylpyrazoles or 5-(2-hy-
droxyphenyl)-1-phenyl-3-styrylpyrazoles afforded 5-[2-(3-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
determination of some types of pyrazoles,[9] we have now
devoted our attention to the synthesis of new 3(5)-(2-
hydroxyphenyl)pyrazoles and some N-substituted deriva-
tives. Some of these compounds were synthesised by treat-
ment of cinnamoyl-(2-hydroxybenzoyl)methanes (or their
enolic forms) with hydrazines, while others were obtained
from DielsϪAlder reactions of the former compounds with
the highly reactive diene ortho-benzoquinodimethane.
These reactions also allowed study of the reaction behav-
iour both of N-substituted or unsubstituted (2-hydroxy-
phenyl)styrylpyrazoles with these dienes and also of the oxi-
dation of the obtained cycloadducts.
Pyrazoles are well known five-membered heterocyclic
compounds possessing interesting biological properties. Be-
cause of their numerous applications in industry, agriculture
and medicine, pyrazoles have long been attracting consider-
able attention, and various procedures for their syntheses
have been developed.[1Ϫ5] As a result, a wide variety of
pyrazole derivatives have been described in the literature. In
the last decade, for instance, C- and/or N-(2-hydroxyphen-
yl)pyrazoles have been used as ultraviolet stabilisers,[6] as
analytical reagents in the complexation of transition metal
ions[7] and also as analgesic agents and as platelet aggre-
gation inhibitors,[8] while other N-substituted pyrazoles are
being used as nonsteroidal anti-inflammatory agents (lona-
zolac) and in the treatment of rheumatoid arthritis (pirazo-
lac). Some well known drugs such as sildenafil (Viagra) and
celecoxib (Celebrex) are also pyrazole derivatives.[4]
Results and Discussion
Chemistry
Our first approach to the synthesis of 3-(2-hydroxyphen-
yl)-5-styrylpyrazole (3a) involved treatment of cinnamoyl(2-
hydroxybenzoyl)methane (1a, existing in equilibrium with
its enolic form 2a) with an excess of hydrazine (formed in
situ by treatment of hydrazinium sulfate with potassium
carbonate), which was added dropwise to the reaction mix-
ture. After some preliminary attempts, the optimal exper-
imental conditions (1:1 mixture of dichloromethane/
methanol as solvent; at room temperature for 3 days) al-
lowed the formation of 3a in 37% yield. As the obtained
result was not satisfactory it was decided to investigate
treatment of 1a with hydrazine hydrate, in methanol at
Knowledge of these useful applications of pyrazoles has
shown that (2-hydroxyphenyl)pyrazoles and their N-substi-
tuted derivatives are important targets for preparation. Fol-
lowing our interest in the synthesis and molecular structure
[a]
Department of Chemistry, University of Aveiro,
3810-193 Aveiro, Portugal
Fax: (internat.) ϩ 351-234-370084
E-mail: arturs@dq.ua.pt
[b]
´
´
Instituto de Quımica Medica,
c/ Juan de la Cierva 3, 28006 Madrid, Spain
Fax: (internat.) ϩ34-91-5644853
E-mail: iqmbe17@iqm.csic.es
4348
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400407
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3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles
FULL PAPER
room temperature, until the disappearance of the starting ture (Scheme 1). The reaction mixture was analysed by thin
material (Scheme 1). 3-(2-Hydroxyphenyl)-5-styrylpyrazole layer chromatography (TLC), and the 3-(2-hydroxyphenyl)-
(3a) was obtained in 42% yield. With diketones 1b and 1c 1-phenyl-5-styrylpyrazoles 5aϪc were isolated in 13, 38 and
(in equilibrium with 2b and 2c) under the same conditions, 12% yields, respectively. As each obtained yield was unsatis-
the corresponding 3-(2-hydroxyphenyl)pyrazoles 3b and 3c factory, some changes in the experimental procedure (quan-
were obtained in 28 and 36% yields. Since the obtained re- tity of phenylhydrazine, reaction time and temperature)
sults werenЈt as good as we had expected, treatment of dike- were made, but the yields of pyrazoles 5aϪc did not in-
tones 1aϪc/2aϪc with hydrazine hydrate in acetic acid (at crease. This prompted us to attempt the reaction in acid
50 °C for 24 h) was also examined. The 3-(2-hydroxyphe- medium (similarly to the treatment of 1aϪc/2aϪc with hy-
nyl)-5-styrylpyrazoles 3a and 3c were obtained in better drazine hydrate, vide supra). Treatment of acetic acid solu-
yields (52% and 58%, respectively) than before, but 3b was tions of cinnamoyl(2-hydroxybenzoyl)methanes 1aϪc/2aϪc
obtained only in 34% yield. In this case 4Ј-methoxy-2-styr- with excess phenylhydrazine for 24 h at 50°C resulted in the
ylchromone (4b)[10] was obtained as a by-product (19% formation of mixtures of the two pyrazole isomers 5aϪc
yield), formed by acid-catalysed cyclodehydration of the di- and 6aϪc, with the 5-(2-hydroxyphenyl)-1-phenyl-3-styryl-
ketone 1b/2b.[11]
pyrazoles 6aϪc being the more abundant (62Ϫ86%), and the
In the first attempt to synthesise 1-phenyl-3(5)-(2- 3-(2-hydroxyphenyl)-1-phenyl-5-styrylpyrazoles 5aϪc being
hydroxyphenyl)-5(3)-styrylpyrazoles (5a or 6a), we also obtained as by-products (1Ϫ2%) (Scheme 1). Treatment of
examined the treatment of cinnamoyl(2-hydroxyben- a monosubstituted hydrazine with an unsymmetrical β-di-
zoyl)methanes 1aϪc/2aϪc with excess phenylhydrazine (ad- ketone resulted in the formation of a mixture of pyrazole
ded in 3 batches, over 4 days) in methanol at room tempera- isomers, in a regioselective manner, since the 3-(2-hydroxy-
Scheme 1
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V. L. M. Silva, A. M. S. Silva, D. C. G. A Pinto, J. A. S. Cavaleiro, J. Elguero
FULL PAPER
phenyl)-1-phenyl-5-styrylpyrazole isomers 5aϪc were ob- chloride,[15] which probably forms a chelate with the
tained in very small quantities. hydroxy oxygen and the free nitrogen of the pyrazole nu-
The reaction between a β-diketone and phenylhydrazine cleus. This complex makes the styryl double bond of pyra-
is apparently a simple reaction, but it conceals a complex zoles 3aϪc more reactive, and cycloadducts 9a and 9b were
mechanistic problem.[12] In this case, the diketones have two indeed obtained in better yields (56 and 53%). In the case
tautomeric forms Ϫ 1aϪc and 2aϪc Ϫ and phenylhydra- of pyrazole 3c there was extensive decomposition in the re-
zine can react initially through the NH or NH2. When the action medium and the cycloadduct 9c was obtained only
reactions between diketones 1aϪc/2aϪc and phenylhydra- in 25% yield.
zine were carried out in methanol, there was a nucleophilic
In order to prepare new pyrazoles with complete and ex-
attack of NH2 at the more electrophilic centre of the dike-
tended aromatic structures, we studied the oxidation of
tone C-1, and only the 5aϪc isomers were obtained, al-
cycloadducts 10aϪc. In initial investigations, dehydrogen-
though in low yields. Under acidic conditions, the more
ation of compounds 10aϪc with five molar equivalent of
basic (NH2) amine group in the phenylhydrazine was pro-
DDQ at reflux in dry 1,4-dioxane over several days resulted
tonated and consequently the nucleophilic attack at the
in the formation of 5-(2-hydroxyphenyl)-3-naphthylpyrazole
more electrophilic centres in the diketones 1aϪc/2aϪc was
derivatives 12aϪc (Scheme 1, E, Method A). The dehydro-
performed by the NH, 5-(2-hydroxyphenyl)-1-phenyl-3-
genation of compound 10b, bearing an electron-donating
substituent at the para position of the phenyl group linked
to the hydroaromatic ring, was faster and gave the expected
compound 12b in better yields than in the other two cases
(Table 1). This can be explained by taking the reaction
mechanism of these oxidation reactions into account. In
styrylpyrazoles 6aϪc therefore being the main reaction
products (62Ϫ86%).
In development of our previous work,[9a] we tried to pre-
pare 3-(2-hydroxyphenyl)pyrazoles 5aϪc in better yields
through reactions between the appropriate 2-styrylchro-
mones and phenylhydrazine. However, we found that the
this case it involves a (benzylic) hydride transfer from com-
styrylchromones were much less reactive than diketones
pounds 10aϪc to DDQ, and the presence of an electron-
donating substituent in the phenyl ring should stabilise the
formed carbocation (C-3ЈЈ). In an attempt to optimise the
and we did not obtain the expected isomers, either from the
reaction in acidic medium or from that in methanol.
With continuing interest in heterocyclic structures and
experimental procedure we found that the presence of a
also in DielsϪAlder cycloaddition reactions of styryl com-
small amount (20% molar equivalent) of p-toluene-
pounds,[10,13] we studied reactions between some of the syn-
sulfonic acid[16] resulted in faster formation of the expected
thesised styrylpyrazoles 3aϪc and 6aϪc and the highly re-
5-(2-hydroxyphenyl)-3-naphthylpyrazoles
12aϪc
with
active ortho-benzoquinodimethane (8; Scheme 1). N-Substi-
tuted pyrazoles 6aϪc reacted with ortho-benzoquinodime-
thane (8), formed in situ by thermal extrusion of sulfur
dioxide from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide
(7),[14] at reflux in 1,2,4-trichlorobenzene over 24 h, to give
cycloadducts 10aϪc in good yields (69Ϫ91%). The styryl
double bond was less reactive when there was an electron-
donating substituent on the para position of the styryl moi-
ety and more reactive if there was an electron-withdrawing
substituent at the same position.
slightly improved reaction yields (Table 1, Scheme 1, E,
Method B).
Other oxidative systems such as MnO2/chlorobenzene,
NBS followed by NEt3, I2/DMSO and chloranil were used,
but were not as efficient as DDQ. It was also found that a
strong oxidant such as DDQ is the most suitable oxidative
agent to perform the dehydrogenation reaction of com-
pounds 10aϪc into 12aϪc.
We also attempted the oxidation of cycloadducts 9aϪc
Pyrazoles 3aϪc are less reactive than N-phenylpyrazoles, by all the methods described, but only unknown (decompo-
since the reactions between 3aϪc and excess ortho-benzo- sition) products were obtained. Only in the oxidation of
quinodimethane (8) took longer (50Ϫ65 h) and gave the 3-(2-hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]-1,2,3,4-
expected cycloadducts 9aϪc in lower yields (48, 24 and tetrahydronaphthyl}pyrazole (9b) with five molar equiva-
48%, respectively), without recovery of any starting mate- lents of DDQ at reflux in dry 1,4-dioxane in the presence
rial. An alternative approach to improve the efficiency of of a small amount (20% molar equivalent) of p-toluenesul-
these DielsϪAlder reactions was the addition of aluminium fonic acid[16] did we succeed in isolating and characterising
Table 1. Yields obtained in the oxidation of cycloadducts 10aϪc with DDQ in dry 1,4-dioxane
E, Method A
R
E, Method B
R
Starting
compounds
Reaction time
(days)
Yield of 12 (%)
Reaction time
(hours)
Yield of 12 (%)
10a
10b
10c
H
OCH3
NO2
5
2
6
12a (25)
12b (59)
12c (17)
H
OCH3
NO2
3
2
7
12a (29)
12b (57)
12c (36)
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3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles
FULL PAPER
the corresponding pyrazole 11b in low yield (13%) benzoquinodimethane (8) and both the 3-(2-hydroxyphe-
(Scheme 1, E, Method B).
nyl)-5-styrylpyrazoles 3aϪc and the 5-(2-hydroxyphenyl)-1-
phenyl-3-styrylpyrazoles 6aϪc were also studied and af-
forded the corresponding cycloadducts 5-[2-(3-aryl-1,2,3,4-
tetrahydronaphthyl)]-3-(2-hydroxyphenyl)pyrazoles 9aϪc
and 3-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-1-phenyl-5-(2-
hydroxyphenyl)pyrazoles 10aϪc, respectively. The oxidation
of these cycloadducts with DDQ in dry 1,4-dioxane was
performed and the new naphthylpyrazoles 11b and 12aϪc
were obtained. All these reactions allowed us to establish
new synthetic methods for novel (2-hydroxyphenyl)pyra-
zoles.
Nuclear Magnetic Resonance
1
The H NMR spectra of the 3-(2-hydroxyphenyl)-5-styr-
ylpyrazoles 3aϪc presented two deshielded broad singlets,
due to the NH and 2Ј-OH resonances, at δ ϭ 10.04Ϫ10.79
and 10.78Ϫ12.81 ppm. The high-frequency value of the
hydroxy proton is due to the intramolecular hydrogen bond
with N2. These intramolecular hydrogen bonds prevent the
prototropy of NH-pyrazoles 3aϪc.
The main criteria by which to distinguish between the
two isomers of 3(5)-(2-hydroxyphenyl)-1-phenyl-5(3)-styryl-
pyrazoles 5aϪc and 6aϪc was the resonance of 2Ј-OH. In
the case of pyrazoles 5aϪc this appears as a singlet at δ
10.68Ϫ10.90 ppm, due to the intramolecular hydrogen
bond between the hydroxy proton and N2 of the pyrazole
nucleus, while in the case of pyrazoles 6aϪc this intramol-
ecular hydrogen bond is not observed and the resonance of
2Ј-OH appears at lower frequencies (δ ϭ 5.30Ϫ5.48 ppm).
Other important features of the NMR spectra of pyra-
zoles 3a-c, 5a-c and 6aϪc are the presence in each of a
singlet due to the resonance of 4-H (δ ഠ 6Ϫ7 ppm) and
doublets due to the resonances of H-α and H-β (δ ഠ 7
Experimental Section
General Remarks: Melting points were measured in a Reichert
Thermovar apparatus fitted with a microscope and are uncor-
rected. NMR spectra were recorded with Bruker AMX and DRX
300 spectrometers (300.13 for 1H and 75.47 MHz for 13C), in
CDCl3 as solvent, if not stated otherwise. Chemical shifts (δ) are
reported in ppm and coupling constants (J) in Hz; internal stand-
ard was TMS. Unequivocal 13C assignments were made with the
aid of 2D gHSQC (or HETCOR) and gHMBC (delays for one-
bond and long-range J C/H couplings were optimised for 145 and
7 Hz, respectively) experiments. Electron impact (EI, 70 eV) MS
were recorded with VG Autospec Q and M spectrometers. Elemen-
tal analyses were obtained with Carlo Erba 1108 and LECO 932
CHNS analysers. Preparative thin-layer chromatography was per-
formed with Merck silica gel (60 DGF254). Column chromatogra-
phy was performed with Merck silica gel 60 (70Ϫ230 mesh). All
other chemicals and solvents used were obtained from commercial
sources and were either used as received or dried by standard pro-
cedures.
3
ppm). The coupling constant values, of JHα,Hβ ഠ 16Ϫ16.5
Hz, indicate the trans configuration in the vinylic moieties.
The connectivities found in the HMBC spectra of these
pyrazoles 3a-c, 5a-c and 6aϪc allowed the unequivocal as-
signments of their C-3 and C-5 carbon resonances (4-H, H-
α, H-β Ǟ C-5 and 4-H and 6Ј-H Ǟ C-3).
The main feature in each of the 1H NMR spectra of
cycloadducts 9aϪc and 10aϪc is the presence of a multiplet
in the aliphatic region of the spectra due to the proton res-
onances of the tetrahydroaromatic ring and the absence of
H-α and H-β resonances. Dehydrogenation of the tetrahy-
droaromatic rings in cycloadducts 9b and 10aϪc induces
some changes in the 1H NMR spectra of the new com-
pounds 11b and 12aϪc. Instead of a multiplet in the ali-
phatic region, we observed two singlets at δ ϭ 7.86Ϫ7.89
and 8.14Ϫ8.48 ppm, due to the resonances of 4ЈЈ-H and
1ЈЈ-H, respectively. The connectivities between 1ЈЈ-H and C-
5 found in the HMBC spectra of 11b and 12aϪc allowed
the unequivocal assignment of this carbon resonance. The
OH and NH resonances of the compounds 9aϪc, 10aϪc,
11b and 12aϪc show behaviour similar to that of the start-
ing pyrazoles 3a-c, 5a-c and 6aϪc.
1-(2-Hydroxyphenyl)-5-phenyl-4-pentene-1,3-diones 1aϪc (which ex-
ist in equilibrium with their enolic forms 2a-c) were obtained as
previously described in the literature.[10]
Synthesis of 3-(2-Hydroxyphenyl)-5-styrylpyrazoles 3aϪc. Method
A: Hydrazine hydrate (4.72 mL, 97.2 mmol) was added to a solu-
tion of the appropriate diketone 1a or 1b/2a or 2b (12.2 mmol) in
methanol (300 mL). The mixture was stirred at room temperature
under nitrogen for 2:30 h. After that, the reaction mixture was
poured into chloroform (250 mL) and washed with an acidic aque-
ous solution (pH 5; 2 ϫ 250 mL). The organic layer was collected
and the solvent was partially removed. The concentrated organic
layer was purified by column chromatography with dichlorometh-
ane as eluent. The solvent was evaporated to dryness and the resi-
due was recrystallised from a mixture of dichloromethane/cyclohex-
ane, giving the expected 3-(2-hydroxyphenyl)-5-styrylpyrazoles (3a
and 3b) as white needles: 3a, 1.34 g (42%) and 3b, 999 mg (28%).
Conclusion
Compound 3c was prepared by the same procedure, but with use
of only 5 molar equivalents of hydrazine hydrate instead of 8 equiv-
alents, and the reaction mixture was stirred at room temperature
Reactions between cinamoyl(2-hydroxybenzoyl)methanes
1aϪc/2aϪc and hydrazine hydrate or phenylhydrazine in under nitrogen for 24 h. The organic layer was purified by column
chromatography with a mixture of dichloromethane/ethyl acetate
(8:2) as eluent. 3-(2-Hydroxyphenyl)-5-(4-methoxystyryl)pyrazole
(3c) was obtained as white needles (1.35 g, 36%).
acetic acid have been studied, and a new synthesis of 3-(2-
hydroxyphenyl)-5-styrylpyrazoles 3aϪc and 5-(2-hydroxy-
phenyl)-1-phenyl-3-styrylpyrazoles 6aϪc has been estab-
lished. Treatment of 1aϪc/2aϪc with phenylhydrazine also
gave 3-(2-hydroxyphenyl)-1-phenyl-5-styrylpyrazoles 5aϪc
Method B: Hydrazine hydrate (0.82 mL, 16.9 mmol) was added to
a solution of the appropriate diketones 1a or 1b/2a or 2b (1.69
as by-products. DielsϪAlder reactions between ortho- mmol) in acetic acid (50 mL). The mixture was heated to 50°C
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V. L. M. Silva, A. M. S. Silva, D. C. G. A Pinto, J. A. S. Cavaleiro, J. Elguero
FULL PAPER
under nitrogen for 24 h. After that period the reaction mixture was
poured into a mixture of ice and water (100 mL). The obtained
solid was removed by filtration, taken up in chloroform (100 mL)
and washed with water (2 ϫ 100 mL). The concentrated organic
layer was purified by column chromatography with dichlorometh-
ane as eluent. The solvent was evaporated to dryness, and the resi-
due was recrystallised from a mixture of dichloromethane/cyclohex-
ane, giving the expected 3-(2-hydroxyphenyl)-5-styrylpyrazole (3a
and 3c) as white needles: 3a, 231 mg (52%) and 3c, 301 mg (58%).
In the reaction between 1b/2b and hydrazine hydrate, the reaction
mixture was purified by preparative TLC, with dichloromethane as
eluent. After several elutions, three spots were collected; the first
one was identified as 4Ј-methoxy-2-styrylchromone (4b; 19.0%), the
second was the expected 3-(2-hydroxyphenyl)-5-(4-methoxystyryl)-
pyrazole (3b; 168 mg, 34%) and the third was the starting material
1b/2b (7%).
121 (7), 106 (11), 91 (7), 77 (8), 72 (6), 58 (10). C17H13N3O3 (307.1):
calcd. C 66.44, H 4.26, N 13.67; found C 65.84, H 4.19, N 13.47.
Synthesis of 3(5)-(2-Hydroxyphenyl)-1-phenyl-5(3)-styrylpyrazoles
5aϪc and 6aϪc: Phenylhydrazine (0.74 mL, 7.51 mmol) was added
to a solution of the appropriate diketone 1a or 1b/2a or 2b (0.75
mmol) in acetic acid (50 mL). The mixture was heated (50°C) under
nitrogen for 21 h. After that period the reaction mixture was
poured into ice and water (100 mL). The obtained solid was re-
moved by filtration, taken up in chloroform (100 mL), washed with
water (2 ϫ 100 mL) and dried (anhydrous sodium sulfate). After
partial concentration in vacuo, the obtained solution was purified
by silica gel thin layer chromatography with a mixture of light
petroleum/ethyl acetate (9:1). After several elutions, two fractions
were collected; the higher Rf fraction was in each case identified as
the 5-(2-hydroxyphenyl)-1-phenyl-3-styrylpyrazole 6aϪc, followed
by the 3-(2-hydroxyphenyl)-1-phenyl-5-styrylpyrazole 5aϪc. The
solvent was evaporated to dryness and the residue in each case was
recrystallised from methanol.
3-(2-Hydroxyphenyl)-5-styrylpyrazole (3a): M.p. 120Ϫ121°C
(recrystallised from a mixture of dichloromethane/cyclohexane). 1H
NMR: δ ϭ 6.78 (s, 1 H, 4-H), 6.94 (dt, J ϭ 7.6, 1.2 Hz, 1 H, 5Ј-
H), 6.98 (d, J ϭ 16.5 Hz, 1 H, H-α), 7.04 (dd, J ϭ 8.0, 1.2 Hz, 1
H, 3Ј-H), 7.12 (d, J ϭ 16.5 Hz, 1 H, H-β), 7.24 (ddd, J ϭ 7.6, 8.0,
1.6 Hz, 1 H, 4Ј-H), 7.32 (tt, J ϭ 7.1, 1.3 Hz, 1 H, 4ЈЈ-H), 7.40 (dd,
J ϭ 8.4, 7.1 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.51 (dd, J ϭ 8.4, 1.3 Hz, 2 H,
2ЈЈ,6ЈЈ-H); 7.61 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 10.10 (br. s, 1 H,
NH), 10.78 (br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 99.7 (CϪ4),
114.3 (C-α), 116.4 (C-1Ј), 117.1 (C-3Ј), 119.4 (C-5Ј), 126.5 (C-6Ј),
126.7 (C-2ЈЈ,6ЈЈ), 128.7 (C-4ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ), 129.4 (C-4Ј), 132.2
(C-β), 135.8 (C-1ЈЈ), 142.0 (C-5), 152.9 (C-3), 155.9 (C-2Ј) ppm. EI-
MS: m/z (rel. int., %) ϭ 262 (22) [Mϩ·], 261 (9) [M Ϫ H]ϩ, 236
(100), 207 (18), 178 (9), 131 (6), 118 (5), 104 (15), 7 (12), 63 (5).
C17H14N2O (262.1): calcd. C 77.84, H 5.38, N 10.68; found C
77.84, H 5.20, N 10.69.
5-(2-Hydroxyphenyl)-1-phenyl-3-styrylpyrazole (6a): Yield 86% (218
mg). M.p. 151Ϫ153°C (recrystallised from methanol). 1H NMR:
δ ϭ 5.48 (s, 1 H, 2Ј-OH), 6.79 (s, 1 H, 4-H), 6.86 (ddd, J ϭ 7.6,
7.4, 1.0 Hz, 1 H, 5Ј-H), 6.95 (dd, J ϭ 8.4, 1.0 Hz, 1 H, 3Ј-H), 7.00
(dd, J ϭ 7.6, 1.7 Hz, 1 H, 6Ј-H), 7.20 (d, J ϭ 16.5 Hz, 1 H, H-α),
7.24Ϫ7.32 (m, 7 H, 4Ј,4ЈЈ,2ЈЈЈ,3ЈЈЈ, 4ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H), 7.26 (d, J ϭ
16.5 Hz, 1 H, H-β), 7.34 (dd, J ϭ 8.4, 7.2 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.54
(dd, J ϭ 8.4, 1.2 Hz, 2 H, 2ЈЈ,6ЈЈ-H) ppm. 13C NMR: δ ϭ 105.8
(C-4), 116.1 (C-3Ј), 117.0 (C-1Ј), 120.0 (C-α), 120.6 (C-5Ј), 124.1
(C-2ЈЈЈ,6ЈЈЈ), 126.2 (C-2ЈЈ,6ЈЈ), 127.4 (C-4ЈЈЈ), 127.9 (C-4ЈЈ), 128.7
(C-3ЈЈ,5ЈЈ), 128.9 (C-3ЈЈЈ,5ЈЈЈ), 130.8 (C-4Ј), 130.85 (C-6Ј), 131.2 (C-
β), 136.9 (C-1ЈЈ), 138.6 (C-5), 139.6 (C-1ЈЈЈ), 151.5 (C-3), 153.2 (C-
2Ј) ppm. EI-MS: m/z (rel. int., %) ϭ 338 (100) [Mϩ·], 337 (94) [M
Ϫ H]ϩ, 321 (2), 310 (2), 261 (3), 246 (4), 234 (7), 217 (4), 196 (13),
180 (4), 169 (4), 128 (3), 115 (5), 91 (5), 77 (18). C23H18N2O (338.1):
calcd. C 81.63, H 5.36, N 8.28; found C 81.34, H 5.34, N 8.12.
3-(2-Hydroxyphenyl)-5-(4-methoxystyryl)pyrazole
(3b):
M.p.
117Ϫ119°C (recrystallised from a mixture of dichloromethane/
1
cyclohexane). H NMR: δ ϭ 3.84 (s, 3 H, 4ЈЈ-OCH3), 6.76 (s, 1 H,
3-(2-Hydroxyphenyl)-1-phenyl-5-styrylpyrazole (5a): Yield 1.3% (3.3
mg). M.p. 182Ϫ184°C (recrystallised from methanol). 1H NMR:
δ ϭ 6.92 (d, J ϭ 16.3 Hz, 1 H, H-α), 6.96 (dt, J ϭ 7.6, 1.0 Hz, 1
H, 5Ј-H), 7.04 (dd, J ϭ 8.0, 1.0 Hz, 1 H, 3Ј-H), 7.04 (s, 1 H, 4-H),
7.22 (d, J ϭ 16.3 Hz, 1 H, H-β), 7.25 (ddd, J ϭ 8.0, 7.6, 1.5 Hz, 1
H, 4Ј-H), 7.20Ϫ7.28 (m, 1 H, 4ЈЈЈ-H), 7.28Ϫ7.39 (m, 3 H,
3ЈЈ,4ЈЈ,5ЈЈ-H), 7.44 (dd, J ϭ 7.6, 2.0 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.52Ϫ7.55
(m, 4 H, 2ЈЈЈ,3ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H), 7.66 (dd, J ϭ 7.6, 1.5 Hz, 1 H, 6Ј-
H), 10.82 (s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 100.5 (C-4), 115.0
(C-α), 116.2 (C-1Ј), 117.2 (C-3Ј), 119.3 (C-5Ј), 125.2 (C-2ЈЈЈ,6ЈЈЈ),
126.5 (C-6Ј), 126.8 (C-2ЈЈ,6ЈЈ), 128.3 (C-4ЈЈЈ), 128.7 (C-4ЈЈ), 128.9
(C-3ЈЈ,5ЈЈ), 129.4 (C-3ЈЈЈ,5ЈЈЈ), 129.5 (C-4Ј), 133.6 (C-β), 136.1 (C-
1ЈЈ), 138.8 (C-1ЈЈЈ), 142.0 (C-5), 151.9 (C-3), 156.1 (C-2Ј) ppm. EI-
MS: m/z (rel. int., %) ϭ 338 (100) [Mϩ·], 337 (30) [M Ϫ H]ϩ, 261
(7), 247 (3), 234 (2), 217 (5), 206 (7), 191 (2), 178 (2), 169 (4), 142
(2), 128 (3), 115 (6), 102 (2), 91 (6), 77 (15), 65 (3). EI-HRMS
(C23H18N2O): calcd. 338.1419; found 338.1419.
4-H), 6.83 (d, J ϭ 16.6 Hz, 1 H, H-α), 6.92 (d, J ϭ 8.8 Hz, 2 H,
3ЈЈ,5ЈЈ-H), 6.93 (ddd, J ϭ 8.2, 7.3, 1.2 Hz, 1 H, 5Ј-H), 7.04 (dd,
J ϭ 8.4, 1.2 Hz, 1 H, 3Ј-H), 7.05 (d, J ϭ 16.6 Hz, 1 H, H-β), 7.24
(dt, J ϭ 8.2, 1.6 Hz, 1 H, 4Ј-H), 7.44 (d, J ϭ 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-
H), 7.60 (dd, J ϭ 7.3, 1.6 Hz, 1 H, 6Ј-H), 10.04 (br. s, 1 H, NH),
10.83 (br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 55.4 (4ЈЈ-OCH3),
99.2 (C-4), 112.1 (C-α), 114.3 (C-3ЈЈ,5ЈЈ), 116.5 (C-1Ј), 117.1 (C-
3Ј), 119.3 (C-5Ј), 126.5 (C-6Ј), 128.0 (C-2ЈЈ,6ЈЈ), 128.6 (C-1ЈЈ), 129.4
(C-4Ј), 131.8 (C-β), 142.3 (C-5), 152.9 (C-3), 160.1 (C-4ЈЈ), 156.0
(C-2Ј) ppm. EI-MS: m/z (rel. int., %) ϭ 292 (100) [Mϩ·], 291 (51)
[M Ϫ H]ϩ, 277 (11), 261 (7) [M Ϫ OCH3)ϩ, 248 (10), 146 (11), 131
(7), 121 (8), 115 (10), 102 (9), 89 (8), 77 (11), 63 (10). C18H16N2O2
(292.1): calcd. C 73.95, H 5.52, N 9.58; found C 74.09, H 5.58,
N 9.62.
3-(2-Hydroxyphenyl)-5-(4-nitrostyryl)pyrazole
(3c):
M.p.
218Ϫ220°C (recrystallised from a mixture of dichloromethane/
1
cyclohexane). H NMR: δ ϭ 6.93 (ddd, J ϭ 7.8, 7.6, 1.0 Hz, 1 H,
5Ј-H), 6.95 (dd, J ϭ 8.0, 1.0 Hz, 1 H, 3Ј-H), 7.19 (s, 1 H, 4-H),
5-(2-Hydroxyphenyl)-3-(4-methoxystyryl)-1-phenylpyrazole
(6b):
7.22 (ddd, J ϭ 8.0, 7.6, 1.6 Hz, 1 H, 4Ј-H), 7.52 (s, 2 H, H-α and Yield 84% (232 mg). M.p. 137Ϫ139°C (recrystallised from meth-
H-β), 7.74 (dd, J ϭ 7.8, 1.6 Hz, 1 H, 6Ј-H), 7.89 (d, J ϭ 7.0 Hz, 2
anol). 1H NMR: δ ϭ 3.84 (s, 3 H, 4ЈЈ-OCH3), 5.48 (s, 1 H, 2Ј-OH),
H, 2ЈЈ,6ЈЈ-H), 8.28 (d, J ϭ 7.0 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 10.79 (br. s, 1 6.76 (s, 1 H, 4-H), 6.85 (dt, J ϭ 7.6, 1.0 Hz, 1 H, 5Ј-H), 6.92 (d,
H, NH), 12.81 (br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 101.4 (C-
J ϭ 8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.95 (d, J ϭ 8.2 Hz, 1 H, 3Ј-H), 7.00
4), 117.4 (C-1Ј), 117.5 (C-3Ј), 120.1 (C-5Ј), 124.9 (C-3ЈЈ,5ЈЈ), 127.5 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 7.10 (d, J ϭ 16.5 Hz, 1 H, H-α),
(C-6Ј), 128.2 (C-2ЈЈ,6ЈЈ), 130.0 (C-4Ј), 130.5 (C-α and C-β), 142.0 7.16 (d, 16.5 Hz, H, H-β), 7.25Ϫ7.31 (m, H,
J
ϭ
1
7
(C-1ЈЈ), 143.1 (C-5), 146.6 (C-4ЈЈ), 148.1 (C-3), 156.9 (C-2Ј) ppm. 4Ј,4ЈЈ,2ЈЈЈ,3ЈЈЈ,4ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H), 7.48 (d, J ϭ 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H)
EI-MS: m/z (rel. int., %) ϭ 307 (100) [Mϩ·], 306 (20) [M Ϫ H]ϩ, ppm. 13C NMR: δ ϭ 55.3 (4ЈЈ-OCH3), 105.6 (C-4), 114.2 (C-
292 (11), 277 (21) [M Ϫ NO2]ϩ, 260 (10), 231 (4), 202 (4), 173 (13),
3ЈЈ,5ЈЈ), 116.1 (C-3Ј), 117.0 (C-1Ј), 117.9 (C-α), 120.6 (C-5Ј), 124.1
www.eurjoc.org
4352
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 4348Ϫ4356

3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles
(C-2ЈЈЈ,6ЈЈЈ), 127.3 (C-4ЈЈЈ), 127.8 (C-2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈЈ,5ЈЈЈ), phenyl)-5-styrylpyrazole 3a or 3b (7.62 ϫ 10Ϫ1 mmol) in 1,2,4-
FULL PAPER
129.7 (C-1ЈЈ), 130.7 (C-4Ј), 130.80 (C-β), 130.84 (C-6Ј), 138.4 (C-
5), 139.6 (C-1ЈЈЈ), 151.9 (C-3), 153.3 (C-2Ј), 159.5 (C-4ЈЈ) ppm. EI-
trichlorobenzene (50 mL) in the presence of aluminium chloride
(0.10 g, 7.62 ϫ 10Ϫ1 mmol). The mixture was heated at reflux under
MS: m/z (rel. int., %) ϭ 369 (33 ) [M ϩ H]ϩ, 368 (100) [Mϩ·], 367 nitrogen for 24 h. After cooling to room temperature, the reaction
(60) [M Ϫ H]ϩ, 353 (6), 324 (2), 276 (2), 264 (6), 247 (2), 233 (3),
218 (2), 208 (3), 196 (13), 184 (6), 165 (3), 152 (3), 139 (2), 121 (2), chloroform (2 ϫ 100 mL). The organic layer was dried (sodium
mixture was poured into water (100 mL) and ice and extracted with
115 (3), 102 (3), 89 (5), 77 (22), 63 (5). C24H20N2O2 (368.2): calcd.
C 78.24, H 5.47, N 7.60; found C 78.16, H 5.46, N 7.59.
sulfate) and concentrated to dryness. The obtained residue was
taken up in light petroleum and purified by column chromatogra-
phy; 1,2,4-trichlorobenzene was eluted with light petroleum and the
reaction products were then eluted with chloroform. The expected
compounds {5-[2-(3-aryl-1,2,3,4-tetrahydronaphthyl)]-3-(2-hydroxy-
phenyl)pyrazoles 9a and 9b} were obtained as white crystals and
recrystallised in each case from a dichloromethane/light petro-
leum mixture.
3-(2-Hydroxyphenyl)-5-(4-methoxystyryl)-1-phenylpyrazole
(5b):
Yield 1.7% (4.69 mg). M.p. 165Ϫ167°C (recrystallised from meth-
anol). 1H NMR: δ ϭ 3.83 (s, 3 H, 4ЈЈ-OCH3), 6.77 (d, J ϭ 16.3
Hz, 1 H, H-α), 6.89 (d, J ϭ 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.95 (dt, J ϭ
7.5, 1.2 Hz, 1 H, 5Ј-H), 7.00 (s, 1 H, 4-H), 7.04 (dd, J ϭ 8.2, 1.2
Hz, 1 H, 3Ј-H), 7.17 (d, J ϭ 16.3 Hz,1 H, H-β), 7.25 (ddd, J ϭ
8.2, 7.5, 1.6 Hz, 1 H, 4Ј-H), 7.38 (d, J ϭ 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H),
7.53Ϫ7.55 (m, 5 H, 2ЈЈЈ,3ЈЈЈ,5ЈЈЈ,4ЈЈЈ,6ЈЈЈ-H), 7.66 (dd, J ϭ 7.5, 1.6
Hz, 1 H, 6Ј-H), 10.90 (s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 55.3
(4ЈЈ-OCH3), 100.0 (C-4), 112.7 (C-α), 114.2 (C-3ЈЈ,5ЈЈ), 116.2 (C-
1Ј), 117.2 (C-3Ј), 119.3 (C-5Ј), 125.2 (C-2ЈЈЈ,6ЈЈЈ), 126.4 (C-6Ј),
128.2 (C-2ЈЈ,6ЈЈ), 128.8 (C-1ЈЈ), 129.3 (C-3ЈЈЈ,5ЈЈЈ), 129.4 (C-4ЈЈЈ and
C-4Ј), 133.1 (C-β), 128.8 (C-1ЈЈ), 142.3 (C-5), 151.8 (C-3), 156.1 (C-
2Ј), 160.0 (C-4ЈЈ) ppm. EI-MS: m/z (rel. int., %) ϭ 369 (39) [M ϩ
H]ϩ, 368 (100) [Mϩ·], 367 (28) [M Ϫ H]ϩ, 353 (5), 337 (14) [M Ϫ
OCH3]ϩ, 325 (2), 324 (3), 277 (2), 261 (8), 247 (4), 236 (7), 217 (2),
204 (4), 191 (2), 184 (7), 165 (2), 131 (2), 121 (4), 115 (3), 102
(2), 91 (5), 77(11), 65 (2). EI-HRMS C24H20N2O2: calcd. 368.1525;
found 368.1516.
3-(2-Hydroxyphenyl)-5-{2-[3-(4-nitrophenyl)]-1,2,3,4-tetrahydro-
naphthyl}pyrazole (6c) was obtained by the same procedure, but in
the absence of aluminium chloride.
3-(2-Hydroxyphenyl)-5-[2-(3-phenyl-1,2,3,4-tetrahydronaphthyl)]-
pyrazole (9a): Yield 56% (156 mg). M.p. 170Ϫ172°C (recrystallised
1
from a dichloromethane/light petroleum mixture). H NMR: δ ϭ
3.16Ϫ3.19 (m, 3 H, 2 ϫ 1ЈЈ-H, 3ЈЈ-H), 3.23Ϫ3.30 (m, 2 H, 2 ϫ 4ЈЈ-
H), 3.38Ϫ3.46 (m, 1 H, 2ЈЈ-H), 6.45 (s, 1 H, 4-H), 6.88 (dt, J ϭ
7.6, 1.0 Hz, 1 H, 5Ј-H), 6.96 (dd, J ϭ 8.2, 1.0 Hz, 1 H, 3Ј-H),
7.15Ϫ7.24 (m, 4 H, 2ЈЈЈ,6ЈЈЈ,3ЈЈЈ,5ЈЈЈ-H), 7.26Ϫ7.33 (m, 6 H,
5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ,4Ј,4ЈЈЈ-H), 7.50 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 9.09
(br. s, 1 H, NH), 10.68 (br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 35.8
(C-4ЈЈ), 37.5 (C-1ЈЈ), 38.3 (C-2ЈЈ), 46.8 (C-3ЈЈ), 99.4 (C-4), 116.6 (C-
1Ј), 116.9 (C-3Ј), 119.1 (C-5Ј), 126.26 (C-6Ј), 126.30 (C-8ЈЈ), 126.4
(C-5ЈЈ), 127.21 (C-4ЈЈЈ), 127.24 (C-2ЈЈЈ,6ЈЈЈ), 128.6 (C-3ЈЈЈ,5ЈЈЈ),
129.0 (C-6ЈЈ,7ЈЈ and C-4Ј), 134.5 (C-10ЈЈ), 135.6 (C-9ЈЈ), 143.7 (C-
1ЈЈЈ), 146.9 (C-5), 151.8 (C-3), 155.8 (C-2Ј) ppm. EI-MS: m/z (rel.
int., %) ϭ 366 (100) [Mϩ·], 365 (5) [M Ϫ H]ϩ, 351 (2), 275 (54),
262 (15), 250 (8), 202 (4), 193 (13), 178 (13), 165 (5), 142 (4), 128
(7), 115 (29), 104 (14), 91 (22), 78 (7), 65 (3). EI-HRMS
(C25H22N2O): calcd. 366.1732, found 366.1721.
5-(2-Hydroxyphenyl)-3-(4-nitrostyryl)-1-phenylpyrazole (6c): Yield
1
62% (178 g). M.p. 211Ϫ213°C (recrystallised from methanol). H
NMR: δ ϭ 5.30 (s, 1 H, 2Ј-OH), 6.82 (s, 1 H, 4-H), 6.88 (dt, J ϭ
7.6, 1.4 Hz, 1 H, 5Ј-H), 6.94 (dd, J ϭ 8.2, 1.4 Hz, 1 H, 3Ј-H), 7.03
(dd,
J ϭ 7.6, 1.7 Hz, 1 H, 6Ј-H), 7.23Ϫ7.33 (m, 7 H,
4Ј,4ЈЈ,2ЈЈЈ,3ЈЈЈ,4ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H), 7.25 (d, J ϭ 16.5 Hz, 1 H, H-β),
7.39 (d, J ϭ 16.5 Hz, 1 H, H-α), 7.65 (d, J ϭ 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-
H), 8.24 (d, J ϭ 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H) ppm. 13C NMR: δ ϭ 106.4
(C-4), 116.2 (C-3Ј), 116.8 (C-1Ј), 120.8 (C-5Ј), 124.2 (C-2ЈЈЈ,6ЈЈЈ and
C-4Ј), 124.1 (C-3ЈЈ,5ЈЈ), 124.7 (C-α), 126.9 (C-2ЈЈ,6ЈЈ), 127.6 (C-
4ЈЈЈ), 128.4 (C-β), 129.0 (C-3ЈЈЈ,5ЈЈЈ), 130.9 (C-4Ј,6Ј), 139.1 (C-5),
139.5 (C-1ЈЈЈ), 143.4 (C-1ЈЈ), 146.9 (C-4ЈЈ), 150.4 (C-3), 153.1 (C-
2Ј) ppm. EI-MS: m/z (rel. int., %) ϭ 384 (25) [M ϩ H]ϩ, 383 (100)
[Mϩ·], 382 (78) [M Ϫ H]ϩ, 366 (2), 353 (13) [M Ϫ NO]ϩ, 336 (18),
319 (2), 307 (2), 290 (5), 279 (3), 261 (2), 247 (3), 233 (4), 217 (3),
202 (3), 196 (16), 180 (4), 168 (3), 135 (2), 115 (2), 102 (2), 91 (4),
77 (20), 65 (2), 58 (30). C23H17N3O3 (383.1): calcd. C 72.05, H 4.47,
N 10.96; found C 71.50, H 4.37, N 10.85.
3-(2-Hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]-1,2,3,4-tetra-
hydronaphthyl}pyrazole (9b): Yield 53% (160 mg). M.p. 156Ϫ157°C
(recrystallised from a dichloromethane/light petroleum mixture).
1H NMR: δ ϭ 3.09Ϫ3.19 (m, 3 H, 2 ϫ 1ЈЈ-H and 3ЈЈ-H), 3.26Ϫ3.49
(m, 3 H, 2ЈЈ-H and 2 ϫ 4ЈЈ-H), 3.78 (s, 3 H, 4ЈЈЈ-OCH3), 6.46 (s, 1
H, 4-H), 6.83 (d, J ϭ 8.3 Hz, 2 H, 3ЈЈЈ,5ЈЈЈ-H), 6.88 (ddd, J ϭ 8.3,
7.6, 0.7 Hz, 1 H, 5Ј-H), 6.97 (dd, J ϭ 8.3, 0.7 Hz, 1 H, 3Ј-H), 7.10
(d, J ϭ 8.3 Hz, 2 H, 2ЈЈЈ,6ЈЈЈ-H), 7.13Ϫ7.23 (m, 5 H, 5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ-
H and 4Ј-H), 7.51 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 9.11 (br. s, 1
H, NH), 10.72 (br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 35.8 (C-
4ЈЈ), 37.8 (C-1ЈЈ), 38.5 (C-2ЈЈ), 45.9 (C-3ЈЈ), 55.2 (4ЈЈЈ-OCH3), 99.4
(C-4), 114.4 (C-3ЈЈЈ,5ЈЈЈ), 116.7 (C-1Ј), 116.9 (C-3Ј), 119.1 (C-5Ј),
126.2 (C-8ЈЈ), 126.3 (C-5ЈЈ), 126.4 (C-6Ј), 128.2 (C-2ЈЈЈ,6ЈЈЈ), 128.6
(C-6ЈЈ,7ЈЈ), 129.1 (C-4Ј), 134.6 (C-10ЈЈ), 135.65 (C-9ЈЈ), 135.7 (C-
1ЈЈЈ), 147.1 (C-5), 151.8 (C-3), 155.9 (C-2Ј), 158.5 (C-4ЈЈЈ) ppm. EI-
MS: m/z (rel. int., %) ؍ 396 (100) [Mϩ·], 395 (7) [M Ϫ H]ϩ, 292
(9), 275 (39), 261 (7), 223 (21), 198 (5), 173 (9), 145 (6), 128 (6),
121 (92), 115 (26), 115 (29), 104 (8), 91 (10), 77 (7), 65 (4). EI-
HRMS (C26H24N2O2): calcd. 396.1838, found 396.1833.
3-(2-Hydroxyphenyl)-5-(4-nitrostyryl)-1-phenylpyrazole (5c): Yield
0.5% (1.44 mg). M.p. 236Ϫ237°C (recrystallised from methanol).
1H NMR: δ ϭ 6.97 (dt, J ϭ 7.6, 1.1 Hz, 1 H, 5Ј-H), 7.04 (s, 1 H,
4-H), 7.07 (d, J ϭ 16.4 Hz, 1 H, H-α), 7.08 (dd, J ϭ 8.3, 1.1 Hz,
1 H, 3Ј-H), 7.36 (d, J ϭ 16.4 Hz, 1 H, H-β), 7.51Ϫ7.61 (m, 6 H,
4Ј,2ЈЈЈ,3ЈЈЈ,4ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H), 7.57 (d, J ϭ 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H),
7.66 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 8.22 (d, J ϭ 8.8 Hz, 2 H,
3ЈЈ,5ЈЈ-H), 10.68 (s, 1 H, 2Ј-OH) ppm. EI-MS: m/z (rel. int., %) ϭ
383 (100) [Mϩ·], 353 (5) [M Ϫ NO]ϩ, 336 (6), 279 (3), 261 (6), 251
(3), 231 (2), 217 (5), 204 (4), 167 (4), 149 (8), 115 (3), 91 (4), 77 (10),
57 (3). EI-HRMS (C23H17N3O3): calcd. 383.1270; found 383.1269.
3-(2-Hydroxyphenyl)-5-{2-[3-(4-nitrophenyl)]-1,2,3,4-tetrahydro-
naphthyl}pyrazole (9c): Yield 48% (150 mg). M.p. 202Ϫ204°C
(recrystallised from a dichloromethane/light petroleum mixture).
1H NMR: δ ϭ 3.15Ϫ3.18 (m, 2 H, 2 ϫ 1ЈЈ-H), 3.22Ϫ3.26 (m, 2 H,
2 ϫ 4ЈЈ-H), 3.35Ϫ3.40 (m, 1 H, 3ЈЈ-H), 3.42Ϫ3.48 (m, 1 H, 2ЈЈ-H),
6.39 (s, 1 H, 4-H), 6.87 (dt, J ϭ 7.6, 1.1 Hz, 1 H, 5Ј-H), 6.96 (dd,
1,3-Dihydrobenzo[c]thiophene 2,2-Dioxide (7): Prepared according
to literature procedures.[14]
Synthesis of 5-[2-(3-Aryl-1,2,3,4-tetrahydronaphthyl)]-3-(2-hydroxy-
phenyl)pyrazoles 9aϪc: 1,3-Dihydrobenzo[c]thiophene 2,2-dioxide J ϭ 8.2, 1.1 Hz, 1 H, 3Ј-H), 7.18 (ddd, J ϭ 8.2, 7.6, 1.6 Hz, 1 H,
(7; 0.19 g, 1.14 mmol) was added to a solution of the 3-(2-hydroxy- 4Ј-H), 7.20Ϫ7.26 (m, 5 H, 5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ-H and 4ЈЈЈ-H), 7.32 (d, J ϭ
Eur. J. Org. Chem. 2004, 4348Ϫ4356
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4353

V. L. M. Silva, A. M. S. Silva, D. C. G. A Pinto, J. A. S. Cavaleiro, J. Elguero
8.6 Hz, 2 H, 2ЈЈЈ,6ЈЈЈ-H), 7.45 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 6Ј-H), 6Ј), 130.52 (C-4Ј), 135.9 (C-10ЈЈ), 136.2 (C-9ЈЈ), 136.7 (C-1ЈЈЈ),
FULL PAPER
8.09 (d, J ϭ 8.6 Hz, 2 H, 3ЈЈЈ,5ЈЈЈ-H), 9.90 (br. s, 2 H, NH and 2Ј-
136.8 (C-5), 139.5 (C-1ЈЈЈЈ), 153.3 (C-2Ј), 156.3 (C-3), 158.0 (C-4ЈЈЈ)
OH) ppm. 13C NMR: δ ϭ 36.1 (C-4ЈЈ), 37.1 (C-1ЈЈ), 38.2 (C-2ЈЈ),
ppm. EI-MS: m/z (rel. int., %) ϭ 472 (87) [Mϩ·], 471 (7) [M Ϫ H]ϩ,
46.6 (C-3ЈЈ), 99.6 (C-4), 116.3 (C-1Ј), 117.0 (C-3Ј), 119.3 (C-5Ј), 457 (4), 364 (6), 351 (100), 337 (5), 275 (5), 263 (4), 250 (17), 236
124.1 (C-2ЈЈЈ,6ЈЈЈ), 126.4 (C-6Ј), 126.7 (C-8ЈЈ), 126.8 (C-5ЈЈ), 128.2 (5), 222 (6), 208 (3), 202 (2), 196 (11), 180 (4), 178 (5), 165 (7), 152
(C-3ЈЈЈ,5ЈЈЈ), 128.6 (C-6ЈЈ), 128.7 (C-7ЈЈ), 129.4 (C-4Ј), 134.2 (C-
(4), 139 (2), 128 (4), 121 (30), 115 (15), 104 (7), 103 (5), 91 (7), 77
10ЈЈ), 134.6 (C-9ЈЈ), 146.4 (C-5), 146.8 (C-1ЈЈЈ), 151.2 (C-4ЈЈЈ), 152.2 (27), 65 (5). C32H28N2O2 (472.2): calcd. C 81.33, H 5.97, N 5.93;
(C-3), 155.7 (C-2Ј) ppm. EI-MS: m/z (rel. int., %) ϭ 411 (100)
[Mϩ·], 410 (3) [M Ϫ H]ϩ, 394 (3), 381 (8) [M Ϫ NO]ϩ, 307 (6), 284
(3), 275 (33), 261 (10), 236 (2), 215 (2), 202 (4), 191 (5), 173 (10),
165 (3), 152 (2), 132 (4), 121 (6), 118 (12), 115 (14), 106 (16), 104
(15), 91 (23). C25H21N3O3 (411.2): calcd. C 72.98, H 5.14, N 10.21;
found C 73.08, H 5.07, N 9.67.
found C 80.65, H 5.91, N 5.84.
5-(2-Hydroxyphenyl)-3-{2-[3-(4-nitrophenyl)-1,2,3,4-tetrahydro-
naphthyl]}-1-phenylpyrazole (10c): Yield 91% (1.50 g). M.p.
207Ϫ209°C (recrystallised from a mixture of dichloromethane/
cyclohexane). 1H NMR: δ ϭ 3.19 (d, J ϭ 7.7 Hz, 2 H, 2 ϫ 1ЈЈ-H),
3.35 (d, J ϭ 7.5 Hz, 2 H, 2 ϫ 4ЈЈ-H), 3.45Ϫ3.59 (m, 2 H, 2ЈЈ,3ЈЈ-
H), 5.04 (s, 1 H, 2Ј-OH), 6.14 (s, 1 H, 4-H), 6.76Ϫ6.78 (m, 2 H,
5Ј,6Ј-H), 6.85 (d, J ϭ 8.2 Hz, 1 H, 3Ј-H), 7.07 (d, J ϭ 8.1 Hz, 2
Synthesis of 3-[2-(3-Aryl-1,2,3,4-tetrahydronaphthyl)]-1-phenyl-5-(2-
hydroxyphenyl)pyrazoles 10aϪc: 1,3-Dihydrobenzo[c]thiophene 2,2-
dioxide (7; 0.82 g, 4.90 mmol) was added to a solution of the appro-
priate 5-(2-hydroxyphenyl)-1-phenyl-3-styrylpyrazole (6aϪc, 3.27
mmol) in 1,2,4-trichlorobenzene (20 mL). The mixture was heated
at reflux under nitrogen for 24 h. After cooling to room tempera-
ture, the reaction mixture was purified by column chromatography;
1,2,4-trichlorobenzene was eluted with light petroleum and the re-
action products were then eluted with dichloromethane. The ex-
pected compounds Ϫ 5-(2-hydroxyphenyl)-1-phenyl-3-[2-(3-phenyl-
1,2,3,4-tetrahydronaphthyl)]pyrazoles 10aϪc Ϫ were obtained as
white crystals and in each case recrystallised from a mixture of
dichloromethane/cyclohexane.
H, 2ЈЈЈЈ,6ЈЈЈЈ-H), 7.16Ϫ7.44 (m,
8
H, 3ЈЈЈЈ,5ЈЈЈЈ,4ЈЈЈЈ-H,
5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ-H and 4Ј-H), 7.42 (d, J ϭ 8.7 Hz, 2 H, 2ЈЈЈ,6ЈЈЈ-H),
8.12 (d, J ϭ 8.7 Hz, 2 H, 3ЈЈЈ,5ЈЈЈ-H) ppm. 13C NMR: δ ϭ 36.7
(C-4ЈЈ), 37.8 (C-1ЈЈ), 40.2 (C-2ЈЈ), 46.6 (C-3ЈЈ), 106.5 (C-4), 115.9
(C-3Ј), 116.8 (C-1Ј), 120.5 (C-5Ј), 124.1 (C-2ЈЈЈЈ,6ЈЈЈЈ), 126.3 (C-
8ЈЈ), 128.6 (C-7ЈЈ), 128.8 (C-2ЈЈЈ,6ЈЈЈ), 128.9 (C-3ЈЈЈ,5ЈЈЈ), 130.6 (C-
6Ј and C-5ЈЈ), 130.64 (C-4Ј), 135.1 (C-10ЈЈ), 135.5 (C-9ЈЈ), 137.7 (C-
5), 139.4 (C-1ЈЈЈ), 146.4 (C-1ЈЈЈЈ), 152.7 (C-4ЈЈЈ), 153.0 (C-2Ј), 155.4
(C-3) ppm. EI-MS: m/z (rel. int., %) ϭ 487 (100) [Mϩ·], 486 (10)
[M Ϫ H]ϩ, 470 (8), 457 (10) [M Ϫ NO]ϩ, 440 (3), 382 (2), 371 (12),
351 (54), 337 (7), 263 (4), 250 (21), 220 (4), 204 (3), 196 (10), 180
(4), 165 (4), 152 (3), 130 (4), 115 (11), 106 (15), 104 (9), 91 (7), 77
(21). C31H25N3O3 (487.2): calcd. C 76.37, H 5.17, N 8.62; found C
76.48, H 5.14, N 8.66.
5-(2-Hydroxyphenyl)-1-phenyl-3-[2-(3-phenyl-1,2,3,4-tetrahydro-
naphthyl)]pyrazole (10a): Yield 87% (1.26 g). M.p. 169Ϫ171°C
(recrystallised from a mixture of dichloromethane/cyclohexane). 1H
NMR: δ ϭ 3.23Ϫ3.49 (m, 6 H, 2 ϫ 1ЈЈ,4ЈЈ-H and 2ЈЈ,3ЈЈ-H), 5.22
(s, 1 H, 2Ј-OH), 6.03 (s, 1 H, 4-H), 6.74 (ddd, J ϭ 7.6, 6.8, 1.0 Hz,
1 H, 5Ј-H), 6.78 (dd, J ϭ 7.6, 2.1 Hz, 1 H, 6Ј-H), 6.89 (dd, J ϭ
8.0, 1.0 Hz, 1 H, 3Ј-H), 7.10 (dd, J ϭ 8.0, 1.8 Hz, 2 H, 2ЈЈЈЈ,6ЈЈЈЈ-
H), 7.10Ϫ7.31 (m, 13 H, 4Ј-H, 5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ-H and 2ЈЈЈ,
6ЈЈЈ,3ЈЈЈ,5ЈЈЈ,4ЈЈЈ,3ЈЈЈЈ,5ЈЈЈЈ,4ЈЈЈЈ-H) ppm. 13C NMR: δ ϭ 36.4 (C-
4ЈЈ), 37.9 (C-1ЈЈ), 40.6 (C-2ЈЈ), 47.0 (C-3ЈЈ), 107.0 (C-4), 115.8 (C-
3Ј), 116.9 (C-1Ј), 120.2 (C-5Ј), 124.2 (C-2ЈЈЈЈ,6ЈЈЈЈ), 125.83 (C-8ЈЈ),
125.87 (C-5ЈЈ), 126.3 (C-4ЈЈЈЈ), 127.1 (C-4ЈЈЈ), 128.0 (C-2ЈЈЈ,6ЈЈЈ),
128.2 (C-3ЈЈЈ,5ЈЈЈ), 128.6 (C-6ЈЈ), 128.7 (C-3ЈЈЈЈ,5ЈЈЈЈ), 128.75 (C-
7ЈЈ), 130.4 (C-6Ј), 130.5 (C-4Ј), 135.9 (C-10ЈЈ), 136.0 (C-9ЈЈ), 136.9
(C-5), 139.5 (C-1ЈЈЈ), 144.7 (C-1ЈЈЈЈ), 153.3 (C-2Ј), 156.1 (C-3) ppm.
EI-MS: m/z (rel. int., %) ϭ 442 (100) [Mϩ·], 441 (17) [M Ϫ H]ϩ,
427 (6), 365 (8), 350 (25), 351 (65), 338 (8), 337 (15), 326 (16), 275
(5), 250 (23), 221 (4), 209 (6), 196 (13), 181 (24), 180 (25), 170 (4),
145 (6), 129 (4), 115 (13), 104 (10), 91 (14), 85 (6), 77 (14), 57 (4).
C31H26N2O (442.2): calcd. C 84.10, H 5.92, N 6.33; found C 83.94,
H 5.92, N 6.31.
Synthesis of 3-[2-(3-Arylnaphthyl)]-5-(2-hydroxyphenyl)-1-phenyl-
pyrazoles 12aϪc. Method A: DDQ (0.36 g, 1.57 mmol) was added
to a solution of the appropriate 5-(2-hydroxyphenyl)-1-phenyl-3-[2-
(3-aryl-1,2,3,4-tetrahydronaphthyl)]pyrazole (10aϪc, 3.15 ϫ 10Ϫ1
mmol) in dry 1,4-dioxane (10 mL). The mixture was heated at re-
flux under nitrogen for several days (10a 5 days, 10b 2 days and
10c 6 days). After that period the solvent was evaporated to dryness
and the solid residue was dissolved in chloroform and washed with
an aqueous solution of potassium hydrogen carbonate. The organic
layer was purified by thin layer chromatography with a light petro-
leum/ethyl acetate mixture as eluent. The 5-(2-hydroxyphenyl)-1-
phenyl-3-[2-(3-arylnaphthyl)]pyrazoles 12aϪc were obtained as
white crystals and were recrystallised in each case from a dichloro-
methane/cyclohexane mixture [12a, 25% (34.5 mg); 12b, 59% (87.0
mg); 12c, 17% (25.9 mg)].
Method B: DDQ (0.19 g, 8.29 ϫ 10Ϫ1 mmol) and p-toluenesulfonic
5-(2-Hydroxyphenyl)-3-{2-[3-(4-methoxyphenyl)-1,2,3,4-tetrahydro- acid (0.026 g, 1.36 ϫ 10Ϫ1 mmol) were added to a solution of the
naphthyl]}-1-phenylpyrazole (10b): Yield 69% (1.06 g). M.p.
appropriate
5-(2-hydroxyphenyl)-1-phenyl-3-[2-(3-aryl-1,2,3,4-
168Ϫ170°C (recrystallised from a mixture of dichloromethane/ tetrahydronaphthyl)]pyrazole (10aϪc, 6.81 ϫ 10Ϫ1 mmol) in dry
cyclohexane). 1H NMR: δ ϭ 3.18Ϫ3.26 (m, 4 H, 2 ϫ 1ЈЈ,4ЈЈ-H), 1,4-dioxane (10 mL). The mixture was heated at reflux under nitro-
3.23Ϫ3.49 (m, 2 H, 2ЈЈ,3ЈЈ-H), 3.79 (s, 3 H, 4ЈЈЈ-OCH3), 4.99 (s, 1 gen for several hours (3 h, 10a; 2 h, 10b and 7 h, 10c). After that
H, 2Ј-OH), 6.01 (s, 1 H, 4-H), 6.74 (ddd, J ϭ 8.0, 6.9, 0.6 Hz, 1 H, period the solid residue was filtered off and washed with chloro-
5Ј-H), 6.81 (dd, J ϭ 6.9, 1.0 Hz, 1 H, 6Ј-H), 6.82 (d, J ϭ 8.6 Hz,
2 H, 3ЈЈЈ,5ЈЈЈ-H), 6.90 (dd, J ϭ 8.4, 0.6 Hz, 1 H, 3Ј-H), 7.17 (d, partially evaporated, and the mixture was purified by column chro-
J ϭ 8.5 Hz, 2 H, 2ЈЈЈЈ,6ЈЈЈЈ-H), 7.18 (d, J ϭ 8.5 Hz, 2 H, 3ЈЈЈЈ,5ЈЈЈЈ- matography: some unknown compounds were eluted with hexane
form. The organic layer was washed with water, the solvent was
H), 7.16Ϫ7.23 (m, 6 H, 4Ј-H, 4ЈЈЈЈ-H and 5ЈЈ,6ЈЈ,7ЈЈ,8ЈЈ-H), 7.25 (d, and then the 5-(2-hydroxyphenyl)-1-phenyl-3-[2-(3-arylnaphthyl)]-
J ϭ 8.6 Hz, 2 H, 2ЈЈЈ,6ЈЈЈ-H) ppm. 13C NMR: δ ϭ 36.5 (C-4ЈЈ), pyrazoles 12aϪc were eluted, with a dichloromethane/hexane mix-
38.1 (C-1ЈЈ), 40.9 (C-2ЈЈ), 46.1 (C-3ЈЈ), 55.3 (4ЈЈЈ-OCH3), 107.0 (C- ture (1:1) in each case. Pyrazoles 12aϪc were obtained as white
4), 113.6 (C-3ЈЈЈ,5ЈЈЈ), 115.9 (C-3Ј), 116.9 (C-1Ј), 120.2 (C-5Ј), 124.2 crystals and were recrystallised in each case from a mixture of di-
(C-2ЈЈЈЈ,6ЈЈЈЈ), 125.8 (C-8ЈЈ), 125.9 (C-5ЈЈ), 127.1 (C-4ЈЈЈЈ), 128.6 (C-
6ЈЈ), 128.78 (C-3ЈЈЈЈ,5ЈЈЈЈ and C-7ЈЈ), 128.8 (C-2ЈЈЈ,6ЈЈЈ), 130.5 (C-
chloromethane/cyclohexane [12a, 29% (86.5 mg); 12b, 57% (181.7
mg); 12c, 36% (11.4 mg)].
4354
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4348Ϫ4356

3(5)-(2-Hydroxyphenyl)-5(3)-styrylpyrazoles
FULL PAPER
5-(2-Hydroxyphenyl)-1-phenyl-3-[2-(3-phenylnaphthyl)]pyrazole
(12a): M.p. 160Ϫ162°C (recrystallised from a mixture of dichloro-
methane/cyclohexane). 1H NMR: δ ϭ 5.03 (s, 1 H, 2Ј-OH), 5.81
Synthesis
of
3-(2-Hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]-
naphthyl}pyrazole (11b): DDQ (0.52 g, 2.30 mmol) and p-tolu-
enesulfonic acid (0.017 g, 9.18 ϫ 10Ϫ2 mmol) were added to a solu-
(s, 1 H, 4-H), 6.75 (ddd, J ϭ 7.4, 6.9, 0.8 Hz, 1 H, 5Ј-H), 6.81 (dd, tion of 3-(2-hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]-1,2,3,4-
J ϭ 7.4, 1.8 Hz, 1 H, 6Ј-H), 6.92 (d, J ϭ 8.0 Hz, 1 H, 3Ј-H), tetrahydronaphthyl}pyrazole (9b, 0.18 g, 4.59 ϫ 10Ϫ1 mmol) in dry
7.16Ϫ7.24 (m,
1
H, 4Ј-H), 7.16Ϫ7.34 (m, 10 H, 2ЈЈЈ,3ЈЈЈ,
dioxane (15 mL). The reaction mixture was heated at reflux under
4ЈЈЈ,5ЈЈЈ,6ЈЈЈ-H and 2ЈЈЈЈ,3ЈЈЈЈ,4ЈЈЈЈ,5ЈЈЈЈ,6ЈЈЈЈ-H), 7.50Ϫ7.56 (m, 2 nitrogen for 17 h. After that period, the DDQ was filtered off and
H, 5ЈЈ,8ЈЈ-H), 7.87Ϫ7.99 (m, 2 H, 6ЈЈ,7ЈЈ-H), 7.89 (s, 1 H, 4ЈЈ-H), washed with chloroform. The organic layer was washed with water
8.48 (s, 1 H, 1ЈЈ-H) ppm. 13C NMR: δ ϭ 109.5 (C-4), 116.0 (C-3Ј), and dried (sodium sulfate), and the solvent was evaporated to dry-
116.5 (C-1Ј), 120.4 (C-5Ј), 124.4 (C-2ЈЈЈЈ,6ЈЈЈЈ), 128.4 (C-3ЈЈЈ,5ЈЈЈ), ness. The obtained residue was purified by thin layer chromatogra-
126.3 (C-5ЈЈ), 126.6 (C-8ЈЈ), 127.3 (C-4ЈЈЈЈ), 127.4 (C-6ЈЈ,4ЈЈЈ), 127.7
phy with hexane for the first elution and then a dichloromethane/
(C-2ЈЈЈ,6ЈЈЈ), 128.0 (C-7ЈЈ), 128.2 (C-1ЈЈ), 129.1 (C-4ЈЈ and C- hexane mixture (1:1). 3-(2-Hydroxyphenyl)-5-{2-[3-(4-methoxy-
3ЈЈЈЈ,5ЈЈЈЈ), 129.9 (C-3ЈЈ), 130.5 (C-4Ј), 130.6 (C-6Ј), 132.7 (C-10ЈЈ), phenyl)]naphthyl}pyrazole (11b) was obtained as a white solid (23.6
133.0 (C-9ЈЈ), 136.8 (C-5), 138.9 (C-2ЈЈ), 139.5 (C-1ЈЈЈ), 141.9 (C-
1ЈЈЈЈ), 152.5 (C-3), 153.2 (C-2Ј) ppm. EI-MS: m/z (rel. int., %) ϭ
mg, 13%) and recrystallised from a dichloromethane/cyclohexane
mixture. M.p. 207Ϫ209°C (recrystallised from a mixture of di-
438 (100) [Mϩ·], 437 (65) [M Ϫ H]ϩ, 421 (2), 361 (2), 351 (6), 331 chloromethane/cyclohexane). 1H NMR: δ ϭ 3.87 (s, 3 H, 4ЈЈ-
(4), 317 (3), 302 (2), 250 (2), 243 (16), 228 (5), 215 (8), 196 (31), OCH3), 6.84 (s, 1 H, 4-H), 6.94 (ddd, J ϭ 8.1, 7.8, 1.1 Hz, 1 H, 5Ј-
180 (4), 167 (2), 152 (3), 118 (2), 104 (3), 91 (4), 77 (26). C31H22N2O
(438.2): calcd. C 84.91, H 5.06, N 6.39; found C 84.54, H 5.05,
N 6.26.
H), 6.96 (dd, J ϭ 6.6, 2.1 Hz, 2 H, 2ЈЈЈ, 6ЈЈЈ-H), 7.02 (dd, J ϭ 8.2,
1.1 Hz, 1 H, 3Ј-H), 7.23 (dt, J ϭ 8.2, 1.6 Hz, 1 H, 4Ј-H), 7.30 (dd,
J ϭ 6.6, 2.1 Hz, 2 H, 3ЈЈЈ,5ЈЈЈ-H), 7.55Ϫ7.58 (m, 2 H, 5ЈЈ,8ЈЈ-H),
7.60 (dd, J ϭ 7.8, 1.6 Hz, 1 H, 6Ј-H), 7.86 (s, 1 H, 4ЈЈ-H), 7.88Ϫ7.94
(m, 2 H, 6ЈЈ,7ЈЈ-H), 8.14 (s, 1 H, 1ЈЈ-H), 9.34 (br. s, 1 H, NH), 10.71
(br. s, 1 H, 2Ј-OH) ppm. 13C NMR: δ ϭ 55.4 (4ЈЈЈ-OCH3), 101.8
(C-4), 114.3 (C-3ЈЈЈ,5ЈЈЈ), 116.5 (C-1Ј), 117.1 (C-3Ј), 119.3 (C-5Ј),
126.5 (C-6Ј), 126.8 (C-5ЈЈ), 127.4 (C-8ЈЈ), 127.7 (C-7ЈЈ), 127.9 (C-
6ЈЈ), 129.2 (C-1ЈЈ), 129.3 (C-4Ј), 130.0 (C-4ЈЈ), 130.5 (C-2ЈЈЈ,6ЈЈЈ),
132.3 (C-9ЈЈ), 133.3 (C-10ЈЈ), 137.2 (C-1ЈЈЈ), 143.4 (C-5), 152.1 (C-
3), 155.98 (C-2Ј), 159.4 (C-4ЈЈЈ) ppm. EI-MS: m/z (rel. int., %) ϭ
392 (100) [Mϩ·], 391 (64) [M Ϫ H]ϩ, 361 (3) [M Ϫ OCH3]ϩ, 256
(6), 202 (10), 196 (5), 189 (6), 91 (6), 71 (6), 57 (15). EI-HRMS
(C26H20N2O2): calcd. 392.1525, found 392.1525.
5-(2-Hydroxyphenyl)-3-{2-[3-(4-methoxyphenyl)naphthyl]}-1-phenyl-
pyrazole (12b): M.p. 156Ϫ158°C (recrystallised from a mixture of
dichloromethane/cyclohexane). 1H NMR: δ ϭ 3.86 (s, 3 H, 4ЈЈЈ-
OCH3), 5.14 (s, 1 H, 2Ј-OH), 5.84 (s, 1 H, 4-H), 6.76 (dt, J ϭ 7.4,
0.6 Hz, 1 H, 5Ј-H), 6.83 (dd, J ϭ 7.4, 1.8 Hz, 1 H, 6Ј-H), 6.93 (dd,
J ϭ 7.7, 0.6 Hz, 1 H, 3Ј-H), 7.23 (ddd, J ϭ 7.7, 7.4, 1.8 Hz, 1 H,
4Ј-H), 6.96 (d, J ϭ 8.5 Hz, 2 H, 3ЈЈЈ,5ЈЈЈ-H), 7.28Ϫ7.38 (m, 8 H,
2ЈЈЈ,4ЈЈЈ6ЈЈЈ-H and 2ЈЈЈЈ,3ЈЈЈЈ,4ЈЈЈЈ,5ЈЈЈЈ,6ЈЈЈЈ-H), 7.49Ϫ7.52 (m, 2 H,
5ЈЈ,8ЈЈ-H), 7.88Ϫ7.96 (m, 2 H, 6ЈЈ,7ЈЈ-H), 7.86 (s, 1 H, 4ЈЈ-H), 8.46
(s, 1 H, 1ЈЈ-H) ppm. 13C NMR: δ ϭ 55.5 (4ЈЈ-OCH3), 109.6 (C-4),
113.5 (C-3ЈЈЈ,5ЈЈЈ), 116.0 (C-3Ј), 116.6 (C-1Ј), 120.4 (C-5Ј), 124.4
(C-2ЈЈЈЈ,6ЈЈЈЈ), 126.2 (C-5ЈЈ), 126.5 (C-8ЈЈ), 127.3 (C-4ЈЈЈЈ), 127.6 (C-
7ЈЈ), 128.2 (C-6ЈЈ), 128.5 (C-1ЈЈ), 128.9 (C-2ЈЈЈ,6ЈЈЈ), 129.0 (C-4ЈЈ),
130.2 (C-3ЈЈ), 130.6 (C-4Ј,6Ј), 138.6 (C-2ЈЈ), 131.0 (C-3ЈЈЈЈ,5ЈЈЈЈ),
132.6 (C-10ЈЈ), 133.1 (C-9ЈЈ), 134.1 (C-1ЈЈЈ), 136.8 (C-5), 139.6 (C-
1ЈЈЈЈ), 152.7 (C-3), 153.3 (C-2Ј), 159.1 (C-4ЈЈЈ) ppm. EI-MS: m/z
(rel. int.) ϭ 468 (100) [Mϩ·], 467 (57) [M Ϫ H]ϩ, 437 (1) [M Ϫ
OCH3)ϩ], 351 (3), 304 (2), 289 (2), 273 (14), 245 (2), 234 (7), 216
(3), 196 (26), 180 (3), 121 (2), 91 (2), 77 (21). C32H24N2O2 (468.2):
calcd. C 82.03, H 5.16, N 5.98; found C 82.23, H 5.16, N 6.08.
Acknowledgments
Thanks are due to the University of Aveiro, ‘‘Fundaca˜o para a
¸
ˆ
Ciencia e Tecnologia’’ and FEDER for funding the Organic Chem-
istry Research Unit and the project POCTI/QUI/38394/2001. One
of us (V. L. M. Silva) also thanks the University of Aveiro for a
M.Sc. grant.
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J. Elguero, in Comprehensive Heterocyclic Chemistry II (Eds.:
5-(2-Hydroxyphenyl)-3-{2-[3-(4-nitrophenyl)naphthyl]}-1-phenyl-
pyrazole (12c): M.p. 286Ϫ287°C (recrystallised from a mixture of
dichloromethane/cyclohexane). 1H NMR: δ ϭ 5.46 (s, 1 H, 2Ј-OH),
6.02 (s, 1 H, 4-H), 6.82 (ddd, J ϭ 7.7, 7.4, 1.0 Hz, 1 H, 5Ј-H), 6.88
(dd, J ϭ 7.7, 1.8 Hz, 1 H, 6Ј-H), 6.78 (dd, J ϭ 7.6, 1.0 Hz, 1 H,
3Ј-H), 7.17Ϫ7.27 (m, 3 H, 4Ј-H, 4ЈЈЈ-H and 4ЈЈЈЈ-H), 7.22 (d, J ϭ
9.5 Hz, 2 H, 2ЈЈЈЈ,6ЈЈЈЈ-H), 7.55 (d, J ϭ 9.5 Hz, 2 H, 3ЈЈЈЈ,5ЈЈЈЈ-H),
7.54Ϫ7.57 (m, 2 H, 5ЈЈ,8ЈЈ-H), 7.88Ϫ7.97 (m, 2 H, 6ЈЈ,7ЈЈ-H), 7.87
(s, 1 H, 4ЈЈ-H), 8.41 (s, 1 H, 1ЈЈ-H) ppm. 13C NMR: δ ϭ 109.5 (C-
4), 116.1 (C-3Ј), 116.7 (C-1Ј), 120.6 (C-5Ј), 123.2 (C-3ЈЈЈ,5ЈЈЈ), 124.1
(C-2ЈЈЈЈ,6ЈЈЈЈ), 127.0 (C-5ЈЈ), 127.1 (C-8ЈЈ), 127.4 (C-4ЈЈЈЈ), 127.9 (C-
7ЈЈ), 128.2 (C-6ЈЈ), 128.9 (C-3ЈЈЈЈ,5ЈЈЈЈ), 129.3 (C-4ЈЈ), 129.5 (C-3ЈЈ),
129.6 (C-1ЈЈ), 130.76 (C-4Ј and C-6Ј), 130.77 (C-2ЈЈЈ,6ЈЈЈ), 132.8 (C-
10ЈЈ), 133.1 (C-9ЈЈ), 138.0 (C-2ЈЈ,5), 128.9 (C-3ЈЈЈЈ,5ЈЈЈЈ), 139.5 (C-
1ЈЈЈЈ), 146.9 (C-4ЈЈЈ), 148.9 (C-1ЈЈЈ), 151.6 (C-3), 153.1 (C-2Ј) ppm.
EI-MS: m/z (rel. int., %) ϭ 483 (100) [Mϩ·], 484 (42) [M Ϫ H]ϩ,
466 (2) [M Ϫ OH]ϩ, 453 (10) [M Ϫ NO]ϩ, 436 (7), 419 (2), 391
(2), 371 (3), 351 (9), 316 (2), 291 (3), 264 (3), 250 (4), 227 (3), 209
(4), 196 (34), 180 (4), 165 (5), 152 (3), 104 (3), 91 (3), 77 (17).
C31H21N3O3 (483.2): calcd. C 76.99, H 4.38, N 8.69; found C 77.16,
H 4.69, N 8.39.
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Received June 9, 2004
4356
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4348Ϫ4356