Reactions of substituted ethyl 1,2,3,4,4′,5′-hexahydrospiro- [naphthalene-2,5′-pyrazole]-3′-carboxylates with halogens

Article abstract of DOI:10.1007/s11178-005-0289-5

Substituted ethyl 1,2,3,4,4′,5′-hexahydrospiro[naphthalene-2, 5′-pyrazole]-3′-carboxylates react with chlorine or N-bromosuccinimide to give spirocyclic substituted 3-halo-4,5-dihydro-3H- pyrazoles which lose nitrogen molecule on heating with formation of substituted spirocyclic 1-halocyclopropane-1-carboxylates. Heating of the title compounds with bromine in acetic acid results in opening of the spiro-fused six-membered ring to afford ethyl 4-aryl-5-[2-(2-carboxyphenyl)ethyl]pyrazole-3-carboxylates.

Full text of DOI:10.1007/s11178-005-0289-5

Russian Journal of Organic Chemistry, Vol. 41, No. 7, 2005, pp. 1036–1042. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005,
pp. 1058–1063.
Original Russian Text Copyright © 2005 by Molchanov, Korotkov, Kopf, Kostikov.
Reactions of Substituted Ethyl 1,2,3,4,4',5'-Hexahydrospiro-
[naphthalene-2,5'-pyrazole]-3'-carboxylates with Halogens
A. P. Molchanov1, V. S. Korotkov1, J. Kopf2, and R. R. Kostikov1
1 St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
2 Institut für anorganische Chemie, Martin-Luter-King Platz 6, D-20146, Hamburg, Germany
Received November 3, 2004
Abstract—Substituted ethyl 1,2,3,4,4',5'-hexahydrospiro[naphthalene-2,5'-pyrazole]-3'-carboxylates react with
chlorine or N-bromosuccinimide to give spirocyclic substituted 3-halo-4,5-dihydro-3H-pyrazoles which lose
nitrogen molecule on heating with formation of substituted spirocyclic 1-halocyclopropane-1-carboxylates.
Heating of the title compounds with bromine in acetic acid results in opening of the spiro-fused six-membered
ring to afford ethyl 4-aryl-5-[2-(2-carboxyphenyl)ethyl]pyrazole-3-carboxylates.
We previously showed that reactions of bi- and
spirocyclic 4,5-dihydropyrazoles with halogenating
agents lead to formation of substituted 3-halo-4,5-di-
hydro-3H-pyrazoles. Thermolysis of the latter is
accompanied by loss of nitrogen molecule to afford
substituted 1-halocyclopropanecarboxylates [1–6]. In
the present work we examined reactions of ethyl
4'-aryl-1-oxo-1,2,3,4,4',5'-hexahydro-1'H-spiro[naph-
thalene-2,5'-pyrazole]-3'-carboxylates Ia–Ic with
chlorine and N-bromosuccinimide and isolated ethyl
4'-aryl-3'-chloro-1-oxo-1,2,3,4,4',5'-hexahydro-3'H-
spiro[naphthalene-2,5'-pyrazole]-3'-carboxylates IIa–
IIc in 44–72% yield and their 3'-bromo-substituted
analogs IIIa–IIIc in 45–61% yield (Scheme 1). Initial
esters Ia–Ic were synthesized by reaction of ethyl
diazoacetate with (E)-2-arylmethylidene-1,2,3,4-tetra-
hydronaphthalen-1-ones [7]
eters, and satisfactory elemental analyses were also
obtained for compounds IIb and IIIc. It should be
noted that spirocyclic pyrazoles IIa–IIc and IIIa–IIIc
slowly decompose even at room temperature. Their
1H NMR spectra contained singlets from the 4'-H
proton at δ 4.3–4.6 ppm, signals from aromatic
protons, and signals from the ethyl and ethylene
13
(CH2CH2) moieties. In the C NMR spectrum of IIb
we observed the following signals, δC, ppm: 14.1
(CH3), 20.1 (CH2), 31.1 (CH2), 53.6 (CH), 64.1 (CH2),
103.2 (C), 104.8 (C), 164.9 (CO), 190.1 (CO); also,
signals from aromatic carbon atoms were present in the
spectrum.
On heating to 80°C, dihydropyrazoles IIa–IIc and
IIIa–IIIc lose nitrogen molecule, thus being converted
into ethyl 3'-aryl-2'-halo-1-oxo-1,2,3,4-tetrahydrospiro-
[naphthalene-2,1'-cyclopropane]-2'-carboxylates IVa–
IVc and Va–Vc in 59–74 and 37–44% yield, respec-
tively (Scheme 2). The structure of compounds IVa–
The structure of compounds IIa–IIc and IIIa–IIIc
was determined on the basis of their spectral param-
Scheme 1.
Hlg
O
O
O
N
N
N
HN
N
N
Hlg
COOEt
COOEt
Cl2, CHCl3
COOEt
or NBS, CHCl3–AcOH
H
H
H
R
R
R
Ia–Ic
IIa–IIc, IIIa–IIIc
II, Hlg = Cl; III, Hlg = Br; R = H (a), Cl (b), Me (c).
1070-4280/05/4107-1036 © 2005 Pleiades Publishing, Inc.

REACTIONS OF SUBSTITUTED ETHYL 1,2,3,4,4',5'-HEXAHYDROSPIRO...
1037
Scheme 2.
fragment was present. These data unambiguously
indicate trans arrangement of the chlorine atom with
respect to the phenyl group and cis orientation of the
former relative to the carbonyl group in the tetra-
hydronaphthalene ring.
Hlg
O
COOEt
H
IIa–IIc, IIIa–IIIc
Cl
O
H
COOCH2CH3
R
H
H
IVa–IVc, Va–Vc
H
H
IV, Hlg = Cl; V, Hlg = Br; R = H (a), Cl (b), Me (c).
IVc and Va–Vc was confirmed by spectral methods
and elemental analysis. The H NMR spectra of IVa–
The spectra of the reaction mixtures obtained by
heating dihydropyrazoles IIa–IIc and IIIa–IIIc con-
tained a set of signals corresponding to a single cyclo-
propane diastereoisomer. On the other hand, by heating
compounds Ib and Id with bromine in acetic acid at
70°C we isolated 33–60% of ethyl 4-aryl-5-[2-(2-car-
boxyphenyl)ethyl]pyrazolecarboxylates VIa and VIb
(Scheme 3). The structure of products VIa and VIb
was proved by the spectral and analytical data. The
1H NMR spectra of VIa and VIb contained triplets
from the methylene protons at δ 2.83–3.19 ppm,
signals from protons in the ethyl group and aromatic
protons, and a broadened signal at δ 13.2–13.5 ppm
from the acid and NH protons. The carbonyl absorp-
tion band appears in the IR spectra at 1730–1740 cm–1,
and stretching vibrations of the O–H bond in the
carboxy group gives rise to absorption at 3340 cm–1.
The structure of compound VIa was unambiguously
proved by the X-ray diffraction data (see figure).
1
IVc and Va–Vc contained singlets from the cyclo-
propane ring proton at δ 3.87–3.93 ppm, as well as
signals from aromatic protons and those in the ethyl
and ethylene groups. Compound IVc displayed the
13
following signals in the C NMR spectrum, δC, ppm:
14.5 (CH3), 21.5 (CH3), 25.0 (CH2), 28.3 (CH2), 39.2
(CH), 45.6 (C), 48.8 (C), 63.2 (CH2), 166.0 (CO),
191.0 (CO); in addition, signals from aromatic carbon
atoms were present. Signals from carbon atoms in the
cyclopropane ring appeared in a stronger field relative
to those belonging to the pyrazole ring carbon atoms in
the spectra of the initial compounds. The IR spectra of
the products contained absorption bands in the region
1690–1740 cm–1 due to stretching vibrations of the
carbonyl groups.
The 1H–1H NOESY spectrum of IVa revealed cross
peaks originating from interaction between protons of
the ester methylene group and proton in the ortho posi-
tion of the phenyl substituent and between the former
and methylene protons in the tetrahydronaphthalene
ring. In addition, we observed a cross peak correspond-
ing to interaction between ortho-proton in the benzene
ring and methylene protons in the tetrahydronaphtha-
lene ring. No cross peak between the proton in the
cyclopropane ring and methylene protons in the ester
Presumably, as in the reaction with N-bromo-
succinimide, 4,5-dihydropyrazoles I are initially con-
verted into 3-bromodihydropyrazoles III. Heating of
compounds III with bromine in acetic acid gives
3H-pyrazole VII which undergoes acyl shift by
analogy with the van Alfen–Hüttel rearrangement.
Acid hydrolysis of tricyclic intermediate VIII leads to
formation of final product VI (Scheme 4).
Scheme 3.
O
COOH
N
HN
H
N
COOEt
Br2, AcOH
N
H
COOEt
R
R
Ib, Id
VIa, VIb
Id, R = NO2; VIa, R = Cl; VIb, R = NO2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

MOLCHANOV et al.
1038
Scheme 4.
O
O
N
N
COOEt
N
Br2
Br2, AcOH
N
COOEt
I
III
VI
Ar
Ar
VII
VIII
Dehydrobromination of esters IIIa–IIIc with
sodium ethoxide in ethanol gave 30–36% of diesters
IXa–IXc (Scheme 5), and hydrolysis of diester IXb
and monoester VIb in ethanol in the presence of sodi-
um ethoxide afforded dicarboxylic acid X (Scheme 6).
The structure of compounds IXa–IXc was confirmed
by spectral methods and elemental analysis. The
1H NMR spectra of IXa–IXc contained triplets from
protons in the ethylene bridge (δ 2.82–3.27 ppm),
signals from aromatic protons, and signals from pro-
tons in the two ester fragments.
Ethyl 4'-aryl-3'-chloro-1-oxo-1,2,3,4,4',5'-hexa-
hydro-3'H-spiro[naphthalene-2,5'-pyrazole]-3'-car-
boxylates IIa–IIc (general procedure). Dry gaseous
chlorine was passed through a solution of 3 mmol of
ester Ia–Ic in 30 ml of anhydrous chloroform at room
temperature until the reaction was complete (TLC).
The solution was evaporated to a volume of 5 ml,
diluted with 10 ml of ethanol, and evaporated again,
and the precipitate was filtered off.
Ethyl 3'-chloro-1-oxo-4'-phenyl-1,2,3,4,4',5'-
hexahydro-3'H-spiro[naphthalene-2,5'-pyrazole]-3'-
carboxylate (IIa). Yield 44%, mp 79–80°C (decomp.).
1H NMR spectrum, δ, ppm: 0.90 t (3H, J = 7 Hz),
2.10 m (1H), 2.74 m (2H), 3.24 m (1H), 4.00 m (2H),
4.41 s (1H), 7.02 m (2H), 7.33–7.36 m (3H), 7.41 d
(1H, J = 7 Hz), 7.44 d (1H, J = 7 Hz), 7.67 t.d (1H, J =
8, 2 Hz), 7.94 d (1H, J = 8 Hz).
EXPERIMENTAL
The IR spectra were obtained on Specord 75IR and
UR-20 spectrometers from 2% solutions in chloro-
form. The 1H and 13C NMR spectra were recorded on a
Bruker DPX-300 instrument at 300.13 and 75.47 MHz,
respectively, using DMSO-d6 as solvent. The products
and reaction mixtures were analyzed by TLC on
Silufol UV-254 plates.
Ethyl 3'-chloro-4'-(4-chlorophenyl)-1-oxo-1,2,3,-
4,4',5'-hexahydro-3'H-spiro[naphthalene-2,5'-pyra-
zole]-3'-carboxylate (IIb). Yield 55%, mp 110°C
(decomp.). 1H NMR spectrum, δ, ppm: 0.92 t (3H, J =
Scheme 5.
COOEt
H
N
N2
NaOEt
N
N1
C5
IIIa–IIIc
C7
C8
C6
C3
COOEt
C4
C9
C10
R
IXa–IXc
R = H (a), Cl (b), Me (c).
Scheme 6.
COOH
H
N
NaOEt
N
VIb, IXb
COOH
Structure of ethyl 5-[2-(2-carboxyphenyl)ethyl]-4-(4-chloro-
phenyl)pyrazole-3-carboxylate (VIa) according to the X-ray
diffraction data.
Cl
X
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

REACTIONS OF SUBSTITUTED ETHYL 1,2,3,4,4',5'-HEXAHYDROSPIRO...
1039
7 Hz), 2.11 m (1H), 2.66 d.t (1H, J = 14, 5 Hz),
2.80 d.t (1H, J = 17, 5 Hz), 3.27 m (1H), 4.03 m (2H),
4.47 s (1H), 7.07 d (2H, J = 9 Hz), 7.44 m (4H), 7.67 t
(1H, J = 7 Hz), 7.93 d (1H, J = 7 Hz). 13C NMR spec-
trum, δC, ppm: 14.1 (CH3), 20.1 (CH2), 31.1 (CH2),
53.6 (CH), 64.1 (CH2), 103.2 (C), 104.8 (C), 128.0
(CH), 128.8 (CH), 129.5 (CH), 130.1 (C), 131.4 (C),
132.0 (CH), 132.5 (CH), 134.2 (C), 135.7 (CH), 144.7
(C), 164.9 (CO), 190.1 (CO). Found, %: C 60.36;
H 4.44; N 6.88. C21H18Cl2N2O3. Calculated, %:
C 60.45; H 4.35; N 6.71.
7 Hz), 2.01 m (1H), 2.67 m (2H), 3.25 m (1H), 3.92 m
(2H), 4.55 s (1H), 7.0 d (2H, J = 9 Hz), 7.40 d (1H, J =
7 Hz), 7.41 d (2H, J = 9 Hz), 7.43 t (1H, J = 7 Hz),
7.65 t (1H, J = 7 Hz), 7.90 d (1H, J = 7 Hz).
Ethyl 3'-bromo-4'-(4-methylphenyl)-1-oxo-1,2,3,-
4,4',5'-hexahydro-3'H-spiro[naphthalene-2,5'-pyra-
zole]-3'-carboxylate (IIIc). Yield 57%, mp 111–
1
112°C. H NMR spectrum, δ, ppm: 0.83 t (3H, J =
7 Hz), 2.03 m (1H), 2.26 s (3H), 2.68 m (2H), 3.22 m
(1H), 3.90 m (2H), 4.42 s (1H), 6.83 d (2H, J = 7 Hz),
7.13 d (2H, J = 7 Hz), 7.39 d (1H, J = 8 Hz), 7.43 t
(1H, J = 8 Hz), 7.66 t (1H, J = 7 Hz), 7.90 d (1H,
J = 8 Hz). Found, %: C 59.79; H 5.08; N 6.29.
C22H21BrN2O3. Calculated, %: C 59.87; H 4.80; N 6.35.
Ethyl 3'-chloro-4'-(4-methylphenyl)-1-oxo-1,2,3,-
4,4',5'-hexahydro-3'H-spiro[naphthalene-2,5'-pyra-
zole]-3'-carboxylate (IIc). Yield 72%, mp 87–88°C
(decomp.). 1H NMR spectrum, δ, ppm: 0.94 t (3H, J =
7 Hz), 2.09 m (1H), 2.27 s (3H), 2.68 m (1H), 2.79 m
(1H), 3.25 m (1H), 4.01 m (2H), 4.36 s (1H), 6.90 d
(2H, J = 8 Hz), 7.15 d (2H, J = 8 Hz), 7.40 d (1H, J =
7 Hz), 7.44 t (1H, J = 7 Hz), 7.67 t (1H, J = 7 Hz),
7.93 d (1H, J = 8 Hz).
Ethyl 3'-aryl-2'-chloro-1-oxo-1,2,3,4-tetrahydro-
spiro[naphthalene-2,1'-cyclopropane]-2'-carbox-
ylates IVa–IVc (general procedure). A solution of
0.3 mmol of ester IIa–IIc in 4 ml of toluene was
heated for 40 min at 80°C (TLC). Gas evolution was
observed. The solvent was distilled off under reduced
pressure, 2 ml of ethanol was added to the residue, and
the precipitate was filtered off and recrystallized from
ethanol.
Ethyl 4'-aryl-3'-bromo-1-oxo-1,2,3,4,4',5'-hexa-
hydro-3'H-spiro[naphthalene-2,5'-pyrazole]-3'-car-
boxylates IIIa–IIIc (general procedure). N-Bromo-
succinimide, 0.6 g (3.3 mmol), was added at room
temperature to a solution of 3 mmol of ester Ia–Ic in
a mixture of 20 ml of anhydrous chloroform and 10 ml
of acetic acid. When the reaction was complete (TLC),
the mixture was stirred for an additional 40 min and
washed with water, a 5% solution of sodium hydrogen
carbonate, and water again. The organic phase was
dried over MgSO4, evaporated to a volume of 5 ml,
diluted with 10 ml of ethanol, and evaporated again,
and the precipitate was filtered off.
Ethyl 2'-chloro-1-oxo-3'-phenyl-1,2,3,4-tetra-
hydrospiro[naphthalene-2,1'-cyclopropane]-2'-car-
boxylate (IVa). Yield 59%, mp 102–103°C. IR spec-
trum, ν, cm–1: 820, 1030, 1140, 1280 s, 1700 v.s,
1
1730 v.s, 2980. H NMR spectrum, δ, ppm: 1.08 t
(3H, J = 7 Hz), 2.31 d.t (1H, J = 14, 3 Hz), 2.68 t.d
(1H, J = 14, 5 Hz), 3.00 m (2H), 3.93 s (1H), 4.10 m
(2H), 7.23 d (2H, J = 7 Hz), 7.32 m (3H), 7.42 d (1H,
J = 7 Hz), 7.43 t (1H, J 8 Hz), 7.64 t.d (1H, J = 7,
1 Hz), 8.01 d (1H, J = 8 Hz). Found, %: C 71.72;
H 5.95. C21H19ClO3. Calculated, %: C 71.64; H 5.74.
Ethyl 3'-bromo-1-oxo-4'-phenyl-1,2,3,4,4',5'-
hexahydro-3'H-spiro[naphthalene-2,5'-pyrazole]-3'-
carboxylate (IIIa). Yield 45%, mp 101–102°C
(decomp.). 1H NMR spectrum, δ, ppm: 0.80 t (3H, J =
7 Hz), 2.01 m (1H), 2.68 m (2H), 3.23 m (1H), 3.87 m
(2H), 4.48 s (1H), 6.96 m (2H), 7.33 m (3H), 7.42 m
(2H), 7.66 t (1H, J = 7 Hz), 7.91 d (1H, J = 8 Hz).
13C NMR spectrum, δC, ppm: 14.0 (CH3), 26.1 (CH2),
31.2 (CH2), 54.3 (CH), 63.4 (CH2), 94.9 (C), 102.7
(C), 127.9 (CH), 128.7 (CH), 129.2 (CH), 129.5 (CH),
130.0 (CH), 130.2 (CH), 131.6 (C), 134.3 (CH), 135.6
(C), 144.5 (C), 165.7 (CO), 190.5 (CO).
Ethyl 2'-chloro-3'-(4-chlorophenyl)-1-oxo-
1,2,3,4-tetrahydrospiro[naphthalene-2,1'-cyclo-
propane]-2'-carboxylate (IVb). Yield 74%, mp 126–
127°C. IR spectrum, ν, cm–1: 810, 1010, 1150, 1250,
1280 s, 1490, 1700 v.s, 1740 v.s, 3030. 1H NMR spec-
trum, δ, ppm: 1.10 t (3H, J = 7 Hz), 2.23 m (1H),
2.70 m (1H), 2.91 m (1H), 3.04 m (1H), 3.91 s (1H),
4.12 q (2H, J = 7 Hz), 7.27 d (2H, J = 8 Hz), 7.39 d
(2H, J = 8 Hz), 7.42 d (1H, J = 8 Hz), 7.43 t (1H, J =
8 Hz), 7.64 t (1H, J = 7 Hz), 8.01 d (1H, J = 8 Hz).
Found, %: C 64.57; H 4.72. C21H18Cl2O3. Calculated,
%: C 64.80; H 4.66.
Ethyl 3'-bromo-4'-(4-chlorophenyl)-1-oxo-1,2,3,-
4,4',5'-hexahydro-3'H-spiro[naphthalene-2,5'-pyra-
zole]-3'-carboxylate (IIIb). Yield 61%, mp 125°C
(decomp.). 1H NMR spectrum, δ, ppm: 0.85 t (3H, J =
Ethyl 2'-chloro-3'-(4-methylphenyl)-1-oxo-
1,2,3,4-tetrahydrospiro[naphthalene-2,1'-cyclo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

MOLCHANOV et al.
1040
78°C. IR spectrum, ν, cm–1: 820, 1030, 1150 s, 1260 s,
propane]-2'-carboxylate (IVc). Yield 62%, mp 100–
101°C. IR spectrum, ν, cm–1: 820, 1030, 1120, 1150 s,
1260, 1290 v.s, 1600, 1690 v.s, 1740 v.s, 2930, 3040.
1H NMR spectrum, δ, ppm: 1.10 t (3H, J = 7 Hz),
2.29 s (3H), 2.33 m (1H), 2.64 m (1H), 2.99 m (2H),
3.87 s (1H), 4.10 m (2H), 7.10 d (2H, J = 8 Hz), 7.15
(2H, J = 8 Hz), 7.41 d (1H, J = 8 Hz), 7.43 t (1H, J =
8 Hz), 7.64 t (1H, J = 7 Hz), 8.00 d (1H, J = 7 Hz).
13C NMR spectrum, δC, ppm: 14.5 (CH3), 21.5 (CH3),
25.0 (CH2), 28.3 (CH2), 39.2 (CH), 45.6 (C), 48.8 (C),
63.2 (CH2), 127.8 (CH), 128.3 (CH), 129.7 (CH),
129.8 (CH), 130.0 (C), 130.2 (CH), 132.4 (C), 135.1
(CH), 137.2 (C), 144.9 (C), 166.0 (CO), 191.0 (CO).
Found, %: C 70.85; H 5.74. C22H21ClO3. Calculated,
%: C 71.64; H 5.74.
1290 v.s, 1320, 1460, 1610, 1690 v.s, 1740 v.s, 2930,
1
3040. H NMR spectrum, δ, ppm: 1.11 t (3H, J =
7 Hz), 2.17 m (1H), 2.29 s (3H), 2.61 m (1H), 3.07 m
(2H), 3.79 s (1H), 4.11 q (2H, J = 7 Hz), 7.15 s (4H),
7.42 d (1H, J = 7 Hz), 7.43 t (1H, J = 7 Hz), 7.64 t
(1H, J = 8 Hz), 8.00 d (1H, J = 8 Hz). 13C NMR spec-
trum, δC, ppm: 14.4 (CH3), 21.5 (CH3), 25.3 (CH2),
28.1 (CH2), 38.3 (C), 38.7 (CH), 43.4 (C), 63.2 (CH2),
127.7 (CH), 128.4 (CH), 129.7 (CH), 129.9 (CH),
130.2 (CH), 132.0 (C), 135.1 (CH), 137.3 (C), 145.0
(C), 166.1 (CO), 191.6 (CO). Found, %: C 63.97;
H 4.94. C22H21BrO3. Calculated, %: C 63.93; H 5.12.
Ethyl 4-aryl-5-[2-(2-carboxyphenyl)ethyl]pyra-
zole-3-carboxylates VIa and VIb (general proce-
dure). A mixture of 1.5 mmol of ester Ib or Id and
0.5 g (3 mmol) of bromine in 20 ml of acetic acid was
heated for 5 h at 70°C (TLC). The mixture was then
poured into water, and the precipitate was filtered off
and recrystallized from ethanol.
Ethyl 3'-aryl-2'-bromo-1-oxo-1,2,3,4-tetrahydro-
spiro[naphthalene-2,1'-cyclopropane]-2'-carbox-
ylates Va–Vc (general procedure). A solution of
0.3 mmol of compound IIIa–IIIc in 4 ml of toluene
was heated for 40 min at 80°C (TLC). Gas evolution
was observed. The solvent was distilled off under
reduced pressure, 2 ml of ethanol was added to the
residue, and the precipitate was filtered off and recrys-
tallized from ethanol.
Ethyl 5-[2-(2-carboxyphenyl)ethyl]-4-(4-chloro-
phenyl)pyrazole-3-carboxylate (VIa). Yield 60%,
mp 211–212°C. IR spectrum, ν, cm–1: 810, 1010, 1040,
1100, 1280, 1300 s, 1450, 1680 s, 1740 v.s, 2600 br,
3040 br, 3360. 1H NMR spectrum, δ, ppm: 1.12 t (3H,
J = 7 Hz), 2.83 t (2H, J = 7 Hz), 3.19 t (2H, J = 7 Hz),
4.12 q (2H, J = 7 Hz), 7.08 m (3H), 7.28 t (1H,
J = 7 Hz), 7.36 m (3H), 7.78 d (1H, J = 7 Hz),
13.17 br.s (2H). Found, %: C 63.57; H 4.91; N 6.83.
C21H19ClN2O4. Calculated, %: C 63.24; H 4.77;
N 7.03.
Ethyl 2'-bromo-1-oxo-3'-phenyl-1,2,3,4-tetra-
hydrospiro[naphthalene-2,1'-cyclopropane]-2'-car-
boxylate (Va). Yield 44%, mp 81–82°C. IR spectrum,
ν, cm–1: 800, 1040, 1150, 1300, 1610, 1700 s, 1750 v.s,
1
3040 s. H NMR spectrum (CDCl3), δ, ppm: 1.23 t
(3H, J = 7 Hz), 2.42 d.d.d (1H, J = 14, 4, 3 Hz), 2.54 m
(1H), 2.98 d.t (1H, J = 17, 3 Hz), 3.33 m (1H), 4.07 s
(1H), 4.19 q (2H, J = 7 Hz), 7.31 m (6H), 7.39 t (1H,
J = 7 Hz), 7.55 t. d (1H, J = 8, 1 Hz) 8.19 d (1H, J =
8 Hz). Found, %: C 63.01; H 4.76. C21H19BrO3. Calcu-
lated %: C 63.17; H 4.80.
Ethyl 5-[2-(2-carboxyphenyl)ethyl]-4-(4-nitro-
phenyl)pyrazole-3-carboxylate (VIb). Yield 33%,
mp 219–220°C. IR spectrum, ν, cm–1: 810, 870, 1010,
1030, 1050, 1090, 1110, 1230, 1300, 1350 v.s, 1450,
Ethyl 2'-bromo-3'-(4-chlorophenyl)-1-oxo-
1,2,3,4-tetrahydrospiro[naphthalene-2,1'-cyclo-
propane]-2'-carboxylate (Vb). Yield 38%, mp 96–
97°C. IR spectrum, ν, cm–1: 800, 1010, 1150, 1300,
1
1600, 1690, 1730 v.s, 3040 br, 3330. H NMR spec-
trum, δ, ppm: 1.12 t (3H, J = 7 Hz), 2.89 m (2H), 3.19 t
(2H, J = 7 Hz), 4.14 q (2H, J = 7 Hz), 7.07 d (1H, J =
7 Hz), 7.27 t (1H, J = 7 Hz), 7.38 m (3H), 7.76 d
(1H, J = 7 Hz), 8.16 d (2H, J = 8 Hz), 13.00 br.s (1H),
13.51 br.s (1H). Found, %: C 61.55; H 4.71; N 10.13.
C21H19N3O6. Calculated, %: C 61.61; H 4.68; N 10.26.
1
1690, 1740, 3030. H NMR spectrum, δ, ppm: 1.11 t
(3H, J = 7 Hz), 2.11 m (1H), 2.69 m (1H), 3.04 m
(2H), 3.83 s (1H), 4.12 q (2H, J = 7 Hz), 7.29 d (2H,
J = 8 Hz), 7.40 d (2H, J = 8 Hz), 7.43 d (1H, J = 7 Hz),
7.44 t (1H, J = 7 Hz), 7.65 t (1H, J = 7 Hz), 8.01 d
(1H, J = 7 Hz). Found, %: C 58.22; H 4.36.
C21H18BrClO3. Calculated, %: C 58.15; H 4.18.
Reaction of ethyl 3'-bromo-4'-(4-chlorophenyl)-
1-oxo-1,2,3,4,4',5'-hexahydro-1'H-spiro[naphtha-
lene-2,5'-pyrazole]-3'-carboxylate (IIIb) with bro-
mine in acetic acid. A mixture of 2 mmol of ester IIIb
and 4 mmol of bromine in 20 ml of acetic acid was
heated for 1.5 h at 70–75°C (TLC). The mixture was
Ethyl 2'-chloro-3'-(4-methylphenyl)-1-oxo-
1,2,3,4-tetrahydrospiro[naphthalene-2,1'-cyclo-
propane]-2'-carboxylate (Vc). Yield 37%, mp 77–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

REACTIONS OF SUBSTITUTED ETHYL 1,2,3,4,4',5'-HEXAHYDROSPIRO...
1041
poured into water, and the precipitate was filtered off
and recrystallized from ethanol. Yield of VIa 80%.
Found, %: C 70.89; H 6.50; N 6.89. C24H26N2O4. Cal-
culated, %: C 70.92; H 6.45; N 6.89.
5-[2-(2-Carboxyphenyl)ethyl]-4-(4-chloro-
phenyl)pyrazole-3-carboxylic acid (X). a. Ester IXb,
0.15 g (0.35 mmol), was added to a solution prepared
from 0.1 g (4.3 mmol) of sodium and 10 ml of ethanol.
The mixture was heated for 2.5 h at 90°C. The solvent
was evaporated, 20 ml of water was added to the
residue, and the mixture was extracted with chloro-
form. The aqueous phase was acidified with con-
centrated hydrochloric acid, and the precipitate was
filtered off. Yield of acid X 55%, mp 256°C.
Ethyl 4-aryl-5-[2-(2-ethoxycarbonylphenyl)
ethyl]pyrazole-3-carboxylates IXa–IXc (general
procedure). Ester IIIa–IIIc, 2 mmol, was added in
portions under stirring at room temperature to a solu-
tion of sodium ethoxide prepared from 0.15 g
(6 mmol) of sodium and 5 ml of anhydrous ethanol.
The solution turned yellow, and the reaction was
complete in 10 min (TLC). The mixture was passed
through a column charged with silica gel using ethyl
acetate as eluent, the eluate was evaporated, and the
precipitate was filtered off.
b. Ester VIa, 0.5 g (1.20 mmol), was added to
a solution prepared from 0.1 g (4.3 mmol) of sodium
and 10 ml of ethanol. The mixture was heated for 2 h
at 90°C, the solvent was distilled off, 20 ml of water
was added to the residue, and the mixture was
extracted with chloroform. The aqueous phase was
acidified with concentrated hydrochloric acid, and the
precipitate was filtered off. Yield 25%. IR spectrum
(KBr), ν, cm–1: 870, 1010, 1100, 1205, 1265, 1285,
Ethyl 5-[2-(2-ethoxycarbonylphenyl)ethyl]-4-
phenylpyrazole-3-carboxylate (IXa). Yield 36%,
mp 131–132°C. IR spectrum, ν, cm–1: 810, 1050, 1090,
1120 s, 1150, 1190, 1270 v.s, 1360, 1380, 1440,
1
1710 v.s, 3010 br, 3410. H NMR spectrum, δ, ppm:
1.10 t (3H, J = 7 Hz), 1.22 t (3H, J = 7 Hz), 2.83 t (2H,
J = 7 Hz), 3.15 t (2H, J = 7 Hz), 4.13 m (4H), 7.08 m
(3H), 7.30 m (4H), 7.43 t (1H, J = 8 Hz), 7.73 d (1H,
J = 8 Hz), 13.44 br.s (1H). Found, %: C 70.38; H 6.15;
N 7.03. C23H24N2O4. Calculated, %: C 70.39; H 6.16;
N 7.14.
1
1310, 1410, 1700 v.s, 2400–3600. H NMR spectrum,
δ, ppm: 2.80 t (2H, J = 8 Hz), 3.19 t (2H, J = 8 Hz),
7.08 d (1H, J = 7 Hz), 7.14 d (2H, J = 8 Hz), 7.28 t
(1H, J = 8 Hz), 7.36 d (2H, J = 8 Hz), 7.40 m (1H),
7.78 d (1H, J = 8 Hz), 12.80 br.s (2H). Found, %:
C 61.35; H 4.21; N 7.28. C19H15ClN2O4. Calculated,
%: C 61.55; H 4.08; N 7.56.
Ethyl 4-(4-chlorophenyl)-5-[2-(2-ethoxycarbo-
nylphenyl)ethyl]pyrazole-3-carboxylate (IXb). Yield
33%, mp 115–116°C. IR spectrum, ν, cm–1: 810, 1020,
1040, 1090, 1110, 1150, 1200, 1270 v.s, 1300, 1450,
1720 v.s, 3030 s, 3420. 1H NMR spectrum (CDCl3), δ,
ppm: 1.27 t (3H, J = 7 Hz), 1.40 t (3H, J = 7 Hz),
2.95 t (2H, J = 8 Hz), 3.27 (2H, J = 8 Hz), 4.28 q (2H,
J = 7 Hz), 4.36 q (2H, J = 7 Hz), 7.11 d (1H, J = 8 Hz),
7.16 d (2H, J = 8 Hz), 7.28 m (2H), 7.37 m (3H),
7.92 d (1H, J = 8 Hz). 13C NMR spectrum, δC, ppm:
14.5 (CH3), 14.6 (CH3), 26.9 (CH2), 34.1 (CH2), 61.2
(CH2), 61.5 (CH2), 122.2 (C), 126.9 (CH), 128.4 (CH),
129.7 (C), 131.0 (CH), 131.4 (CH), 132.0 (CH), 132.6
(CH), 133.6 (C), 143.0 (C), 162.0 (CO), 168.0 (CO).
Found, %: C 64.96; H 5.58; N 6.63. C23H23ClN2O4.
Calculated, %: C 64.71; H 5.43; N 6.56.
X-Ray diffraction data for compound (VIa).
C21H19ClN2O4. M 398.83. Triclinic crystals, space
group P-1 (no. 2); unit cell parameters: a = 7.0326(7),
b = 7.3013(7), c = 20.636(2) Å; α = 99.25(0), β =
91.58(0), γ = 110.26(0)°; V = 997.15(16) Å3; Z = 2; d =
1.355 g/cm3; μ = 0.078 mm–1; F(000) = 912; irradia-
tion source MoKα, λ = 0.71073 Å, graphite monochro-
mator. Below are given the bond lengths (Å) and bond
angles (deg): N1–N2 1.342(3), N1–C5 1.336(3), N2–C3
1.350(3), C3–C4 1.383(3), C3–C6 1.494(3), C4–C5
1.410(3), C4–C9 1.481(3), C5–C10 1.480(3), C6–C7
1.538(3), C7–C8 1.511(3), N1N2C3 113.55(15), C5N1N2
104.31(16), N1C5C4 111.39(18), N2C3C4 105.97(16),
C3C4C5 104.78(18), N1C5C10 118.50(18), C4C3C6
131.65(19), C5C4C9 127.41(15). The complete set of
crystallographic data was deposited to the Cambridge
Crystallographic Data Center (entry no. 255055).
Ethyl 5-[2-(2-ethoxycarbonylphenyl)ethyl]-4-(4-
methylphenyl)pyrazole-3-carboxylate (IXc). Yield
30%, mp 118–119°C. IR spectrum, ν, cm–1: 810, 1030,
1090, 1120, 1160, 1190, 1260 v.s, 1440, 1710 v.s,
3000 br, 3430. 1H NMR spectrum, δ, ppm: 1.12 t (3H,
J = 7 Hz), 1.22 t (3H, J = 7 Hz), 2.31 s (3H), 2.82 br.s
(2H), 3.14 t (2H, J = 8 Hz), 4.16 m (4H), 6.94 br.m
(2H), 7.11 br.m (3H), 7.30 t (1H, J = 8 Hz), 7.43 t (1H,
J = 8 Hz), 7.73 d (1H, J = 8 Hz), 13.35 br.s (1H).
The authors are grateful to the Foundation of Prof.
A. de Meijere (Georg-August Universität, Göttingen,
Germany) for providing a personal research grant to
V.S. Korotkov.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

MOLCHANOV et al.
4. Molchanov, A.P., Stepakov, A.V., and Kostikov, R.R.,
1042
REFERENCES
Russ. J. Org. Chem., 2002, vol. 38, p. 264.
5. Molchanov, A.P., Stepakov, A.V., Boitsov, V.M., Kopf, J.,
and Kostikov, R.R., Russ. J. Org. Chem., 2002, vol. 38,
p. 1797.
1. Molchanov, A.P., Stepakov, A.V., and Kostikov, R.R.,
Russ. J. Org. Chem., 2001, vol. 37, p. 128.
2. Molchanov, A.P., Stepakov, A.V., Kostikov, R.R., and
6. Molchanov, A.P., Stepakov, A.V., Boitsov, V.M., Kopf, J.,
and Kostikov, R.R., Russ. J. Org. Chem., 2003, vol. 39,
p. 108.
Baird, M.S., Synlett, 2000, p. 219.
3. Molchanov, A.P., Stepakov, A.V., Boitsov, V.M., and
Kostikov, R.R., Russ. J. Org. Chem., 2002, vol. 38,
p. 1666.
7. Molchanov, A.P., Korotkov, V.S., and Kostikov, R.R.,
Russ. J. Org. Chem., 2004, vol. 40, p. 470.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005