Reactions of aliphatic diazo compounds: III. Reaction of ethyl diazoacetate with 1,3-diarylpropenones

Article abstract of DOI:10.1023/A:1013874431574

Ethyl diazoacetate adds to 1,3-diarylpropenones in a regioselective fashion to give intermediate 4,5-dihydro-3W-pyrazole derivative; 1,3-hydride shift in the latter leads to formation of isomeric ethyl 4-aryl-5-aroyl-4,5-dihydro-1H-pyrazole-3-carboxylate

Full text of DOI:10.1023/A:1013874431574

Russian Journal of Organic Chemistry, Vol. 37, No. 11, 2001, pp. 1517 1521. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 11, 2001,
pp. 1593 1597.
Original Russian Text Copyright
2001 by Molchanov, Lykholai, Kostikov.
Reactions of Aliphatic Diazo Compounds: III.* Reaction
of Ethyl Diazoacetate with 1,3-Diarylpropenones**
A. P. Molchanov, A. N. Lykholai, and R. R. Kostikov
St. Petersburg State University, Universitetskii pr. 2, St. Petersburg, 198904 Russia
Received April 24, 2001
Abstract Ethyl diazoacetate adds to 1,3-diarylpropenones in a regioselective fashion to give intermediate
4,5-dihydro-3H-pyrazole derivative; 1,3-hydride shift in the latter leads to formation of isomeric ethyl 4-aryl-
5-aroyl-4,5-dihydro-1H-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-1H-pyrazole-5-car-
boxylate at a ratio of 5: 1. Thermolysis of these products is not stereospecific; as a result, three isomeric
substituted ethyl cyclopropanecarboxylates and 2-pyranone derivative are formed.
Although 1,3-dipolar cycloaddition reactions of
diazo compounds with unsaturated compounds pos-
sessing electron-acceptor groups were known for
a long time, in some cases the structure of the adducts
was not established unambiguously [2]. For example,
Kohler and Steele [3] showed that the reaction of
ethyl diazoacetate (I) with 1,3-diphenylpropenone
(IIa) yields ethyl 5-benzoyl-4-phenyl-4,5-dihydro-
1H-pyrazole-3-carboxylate, whereas in the more recent
study [4] the same product was assigned the structure
of ethyl 3-benzoyl-4-phenyl-4,5-dihydro-1H-pyrazole-
5-carboxylate.
We have examined the reactions of ester I with
1,3-diarylpropenones IIa IIi. By heating of a mixture
of ethyl diazoacetate (I) with 1,3-diphenylpropenone
(IIa) in heptane for 7 h at 75 C we obtained isomeric
dihydropyrazoles IIIa and IVa which were isolated
in 36 and 8% yield, respectively (Scheme 1). The
structure of the products was determined on the basis
of their elemental compositions (Table 1) and spectral
Scheme 1.
II IV, R = R = H (a); R = H, R = 4-Me (b), 4-MeO (c), 3-Br (d), 4-Br (e), 2-Cl (f); R = H, R = 4-MeO (g); R = 4-MeO,
R = 4-Cl (h); R = 3-Br, R = 4-Cl (i).
____________
*
For communication II, see [1].
**
This study was financially supported by the Ministry of
Education of the Russian Federation (project no. E00-5-263).
1070-4280/01/3711-1517$25.00 2001 MAIK Nauka/Interperiodica

1518
MOLCHANOV et al.
observed for compound IIIa:
260 and 326 nm
for IVa and 248 and 290 nm fomr aIxIIa. This indicates
a more extended conjugation chain in molecule IVa.
1
The H NMR spectrum of pyrazole IIIa contains two
doublets at 4.49 and 5.22 ppm (J = 4 Hz). In the
spectrum of IVa the pyrazole ring protons give two
doublets at 4.40 and 4.95 ppm (J = 4 Hz); also,
signals from the ethyl group, aromatic rings, and NH
group are present. The 13C NMR spectra of IIIa and
IVa are consistent with the assumed structures.
In order to prove the structure of products IIIa and
IVa more rigorously, diphenylpropenone IIa was
brought into reaction with ethyl diazoacetate-d [5].
The reaction afforded two products, one of which had
physical properties and spectral parameters similar
to those of IIIa. The other product showed in the
1H NMR spectrum a singlet from 4-H of the pyrazole
ring, indicating the presence of deuterium on the
neighboring carbon atom to which the ester group is
attached. This means that the second product has
structure VI:
Fig. 1. 1H 1H NOESY spectrum of ethyl 5-benzoyl-4-
phenyl-4,5-dihydro-1H-pyrazole-3-carboxylate (IIIa).
1
The 1H H NOESY spectrum of isomer IIIa
(Fig. 1) displayed a cross peak due to coupling of
1
1
the NH proton with CHCOPh. In the H H NOESY
spectrum of isomer IVa (Fig. 2) we observed cross
peaks corresponding to coupling between CHCO2Et
and NH protons and between the former and ortho-
protons of the phenyl (but not benzoyl) group. These
data allowed us to rule out alternative structures of
ethyl 4-benzoyl-5-phenyl-4,5-dihydro-1H-pyrazole-3-
carboxylate and ethyl 4-benzoyl-3-phenyl-4,5-dihydro-
1H-pyrazole-5-carboxylate.
The oxidation of compounds IIIa and IVa with
bromine gave ethyl 3-benzoyl-4-phenylpyrazole-5-
carboxylate (VII) whose structure was established
on the basis of its spectral parameters and published
data [4]:
Fig. 2. 1H 1H NOESY spectrum of ethyl 3-benzoyl-4-
phenyl-4,5-dihydro-1H-pyrazole-5-carboxylate (IVa).
data (Table 2). In the IR spectra of IIIa and IVa we
1
observed absorption bands typical of NH (3400 cm )
1
and C O groups (1700 and 1740 cm ). The absorp-
tion maxima in the UV spectrum of IVa are displaced
to the long-wave region as compared to those
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 11 2001

REACTIONS OF ALIPHATIC DIAZO COMPOUNDS: III.
1519
Table 1. Yields, melting points, and elemental analyses of compounds IIIa IIIi, IVa, VIII, IXa, IXb, and XIIb
Found, %
H
Calculated, %
H
Comp.
no.
Yield, %
mp,
C
Formula
C
N
C
N
8.69
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IVa
VIII
IXa
IXb
XIIb
36
47
15
62
16
11
49
27
46
8
142
70.66
71.32
68.23
56.85
56.89
63.83
62.20
62.03
52.41
70.76
64.07
81.42
64.23
62.28
5.76
6.02
5.65
4.46
4.30
4.68
5.71
5.01
3.70
5.62
4.37
6.15
4.60
3.41
8.66
8.33
7.87
6.89
6.87
7.77
7.95
7.28
6.38
8.72
7.72
C19H18N2O3
C20H20N2O3
C20H20N2O4
C19H17BrN2O3
C19H17BrN2O3
C19H17ClN2O3
C20H20N2O4
C20H19ClN2O4
C19H16BrClN2O3
C19H18N2O3
C19H15ClN2O3
C19H18O3
70.80
71.43
68.18
56.86
56.86
63.90
68.18
62.09
52.35
70.80
64.31
81.63
64.34
62.38
5.59
5.95
5.68
4.24
4.24
4.77
5.68
4.95
3.67
5.59
4.23
6.12
4.55
3.36
147
158
175
131
124
149
137
151
102
181
86
8.33
7.95
6.98
6.98
7.80
7.95
7.24
6.43
8.69
7.89
20
11
16
9
94
119
C19H17BrO3
C17H11BrO2
Thus, the reaction of ethyl diazoacetate with 1,3-di-
phenylpropenone follows the Auwers pattern and
regioselectively yields 4,5-dihydro-3H-pyrazole (V);
1,3-hydride shift in the latter leads to formation of
isomeric 4,5-dihydro-1H-pyrazole derivatives IIIa and
IVa at a ratio of 5:1. In the reactions of ester I with
1,3-diarylpropenones Ib Ii we succeeded in isolating
only the major products, pyrazoles IIIb IIIi. Their
structure was established on the basis of their ele-
mental compositions (Table 1) and spectral parameters
the reaction of ethyl diazoacetate with 3-(2-chloro-
phenyl)-1-phenylpropenone (IIf), apart from products
IIIf and IVf, 20% of ethyl 3-benzoyl-4-(2-chloro-
phenyl)pyrazole-5-carboxylate (VIII) was isolated.
It is known that thermolysis of dihydropyrazoles is
a method for preparation of cyclopropane derivatives
[6]. According to the data of [3, 7], thermolysis of
compound IIIa leads to formation of substituted
2-pyranone XIIa and ethyl 2-benzoyl-3-phenylcyclo-
propanecarboxylate whose steric structure was not
established. By heating of dihydropyrazoles IIIa and
IIId for 75 min at 220 C, followed by separation of
the reaction mixture by column chromatography, we
isolated cyclopropanecarboxylates IXa, IXb, and Xa
and 2-pyranones XIIa and XIIb (Scheme 2).
1
(Table 2). Compounds IIIb IIIi showed in the H
NMR spectra doublet signals at 4.40 4.48 and 5.13
5.22 ppm (CDCl3), J = 4 Hz, from protons at C4 and
C5 of the pyrazole ring, which are arranged trans
1
with respect to each other. The H NMR spectra of
1
the reaction mixtures obtained from ethyl diazoacetate
and 1,3-diarylpropenones also contained signals from
4-H and 5-H of isomeric pyrazoles IVb IVi at 4.40
and 5.00 ppm (J = 4 Hz). The signal positions and
isomer ratios III:IV are given in Experimental. In
The H NMR spectrum of IXa contained three
signals from the cyclopropane ring ptotons at 2.65
(J1 = 6, J2 = 10 Hz), 3.11 (J1 = 6, J2 = 10 Hz), and
3.39 ppm (J1 = 6, J2 = 7 Hz). Compound Xa showed
in the spectrum signals at 2.89 (J1 = 5, J2 = 10 Hz),
Scheme 2.
R = H (a), 3-Br (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 11 2001

1520
MOLCHANOV et al.
Table 2. IR and 1H NMR spectra of compounds IIIa IIIi, IVa, VI, VIII, IXa, IXb, Xa, and XIIb
Comp.
no.
1
IR spectrum, , cm
1H NMR spectrum,a , ppm (J, Hz)
IIIab 1130, 1250, 1350, 1580, 1690, 1.25 t (3H, 7), 4.11 q (2H, 7), 4.49 d (1H, 4), 5.22 d (1H, 4), 7.03 s (1H),
1710, 3040, 3370 7.31 7.72 (8H), 7.92 d (2H, 7)
1130, 1250, 1350, 1580, 1690, 1.09 t (3H, 7), 4.02 q (2H, 7), 4.31 d (1H, 4), 5.42 d (1H, 4), 7.07 d (2H, 8),
1710, 3040, 3370 7.18 d (2H, 8), 7.55 m (2H), 7.70 m (1H), 7.90 m (2H), 8.91 s (1H)
1120, 1190, 1260, 1330 1600, 1.10 t (3H, 7), 3.72 s (3H), 4.00 q (2H, 7), 4.30 d (1H, 4), 5.40 d (1H, 4),
1690, 1710, 3040, 3370 6.93 d (2H, 8), 7.11 d (2H, 8), 7.53 7.70 (3H), 7.90 m (2H), 8.83 s (1H)
1130, 1250, 1350, 1580, 1690, 1.08 t (3H, 7), 4.04 q (2H, 7), 4.44 d (1H, 4), 5.58 d (1H, 4), 7.12 7.78 (7H),
1710, 3040, 337 7.90 d (2H, 7), 9.07 s (1H)
1130, 1250, 1350, 1580, 1690, 1.20 t (3H, 7), 4.11 q (2H, 7), 4.45 d (1H, 4), 5.18 (1H, 4), 7.03 s (1H), 7.20
1710, 3040, 3370 7.71 (7H), 7.80 d (2H, 7)
1130, 1260, 1350, 1590, 1690, 1.24 t (3H, 7), 4.20 q (2H, 7), 4.45 d (1H, 4), 5.10 d (1H, 4), 7.03 7.60 (7H),
1710, 3040, 3370 8.00 d (2H, 7), 9.68 s (1H)
1120, 1190, 1260, 1330, 1600, 1.08 t (3H, 7), 3.86 s (3H), 4.00 q (2H, 7), 4.35 d (1H, 4), 5.42 d (1H, 4),
1690, 1710, 3040, 3370 7.08 d (2H, 7), 7.30 7.45 (3H), 7.87 d (2H, 8), 8.91 s (1H)
1100, 1190, 1260, 1340, 1590, 1.24 t (3H, 7), 3.82 s (1H), 4.16 q (2H, 7), 4.40 d (1H, 4), 5.13 d (1H, 4),
1690, 1710, 3040, 3370 6.93 d (2H, 8), 6.95 s (1H), 7.28 d (2H, 8), 7.49 d (2H, 8), 7.82 d (2H, 8)
1130, 1250, 1350, 1580, 1690, 1.21 t (3H, 7), 4.18 q (2H, 7), 4.41 d (1H, 4), 5.18 d (1H, 4), 7.00 s (1H),
1710, 3040, 3370 7.20 7.60 (6H), 7.81 d (2H, 7)
IVac 1110, 1280, 1410, 1650, 1735, 1.35 t (3H, 7), 4.28 q (2H, 7), 4.40 d (1H, 4), 4.95 d (1H, 4), 7.01 s (1H),
3050, 3380 7.24 7.59 (8H), 8.13 d (2H, 7)
1110, 1280, 1410, 1650, 1735, 1.35 t (3H, 7), 4.28 q (2H, 7), 4.40 d (0.1H, 4), 4.95 s (1H), 7.01 s (1H),
3050, 3380 7.30 7.60 (8H), 8.13 d (2H, 7)
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
VI
VIII 1130, 1250, 1350, 1690, 1710, 1.12 t (3H, 7), 4.18 q (2H, 7), 7.30 8.10 (9H), 14.80 br.s (1H)
3040, 3370
IXa
IXb
Xa
1220, 1310, 1450, 1730
1.14 t (3H, 7), 2.66 d.d (1H, 10, 6), 3.11 d.d (1H, 10, 6), 3.39 d.d (1H, 7, 6),
4.10 q (2H, 7), 7.18 7.65 (8H), 8.06 d (2H, 7)
1220, 1310, 1450, 1680, 1730 1.14 t (3H, 7), 2.65 d.d (1H, 10, 6), 3.10 d.d (1H, 10, 6), 3.36 d.d (1H, 7, 6),
4.10 q (2H, 7), 7.10 7.70 (7H), 8.07 d (2H, 7)
1.08 t (3H, 7), 2.89 d.d (1H, 10, 5), 3.29 d.d (1H, 10, 6), 3.87 d.d (1H, 6, 5),
4.02 q (2H, 7), 7.10 7.70 (8H), 8.16 d (2H, 7)
XIIb 1540, 1630, 1720, 3040
6.47 s (1H), 6.92 s (1H), 7.34 7.75 (9H)
a
1
The H NMR spectra of compounds IIIb, IIIc, IIId, IIIf, and IIIg were recorded in DMSO-d6, and of the others, in CDCl3.
13C NMR spectrum, C, ppm: 14.0 (CH3), 54.7 (CH), 61.2 (CH2), 73.5 (CH), 127.5, 128.0, 128.9, 129.0, 129.3, 132.7, 134.1, 139.1,
161.2 (C O), 195.6 (C O); UV spectrum, max, nm (log ): 248 (4.17), 290 (4.01).
b
c
13C NMR spectrum, C, ppm: 13.9 (CH3), 53.4 (CH), 62.1 (CH2), 69.4 (CH), 127.0, 127.4, 127.9, 128.8, 129.2, 136.7, 139.4,
171.1 (C O), 186.4 (C O); UV spectrum, max, nm (log ): 260 (3.89), 326 (4.08).
1
3.29 (J1 = 6, J2 = 10 Hz), and 3.87 ppm (J1 = 5, J2 =
observed in the H NMR spectrum of the thermolysis
products of dihydropyrazole IIId. In both cases the
ratio IX:X:XI:XII was 2:1:1:1. Thus the ther-
molysis of compounds III is not stereospecific.
6 Hz). The spectral data coincide with those reported
1
for the corresponding methyl esters [8]. In the H
NMR spectrum of the product mixture obtained by
thermolysis of compound IIIa we also observed CH
signals from one more isomeric cyclopropane ester
XI, , ppm (J, Hz): 3.23 (5, 6), 3.35 (6, 10), 3.57
(5, 10); by analogy with the spectrum of methyl t-2-
benzoyl-t-3-phenylcyclopropanecarboxylate [9], prod-
uct XI was assigned the trans,trans-configuration.
Analogous cyclopropane proton signals were also
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from 2% solutions in chloroform. The H
NMR spectra were obtained on a Bruker DPX-300
instrument (300 MHz) from 2% solutions in CDCl3
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 11 2001

REACTIONS OF ALIPHATIC DIAZO COMPOUNDS: III.
1521
or DMSO-d6. The UV spectra were measured on
a Specord UV-Vis spectrophotometer.
by volume) as eluent to isolate 20 mg of ethyl t-2-ben-
zoyl-c-3-phenylcyclopropanecarboxylate (Xa).
Ethyl 5-benzoyl-4-phenyl-4,5-dihydro-1H-pyra-
zole-3-carboxylate (IIIa). 1,3-Diphenylpropenone
(IIa), 10 g (0.05 mol), was dissolved in 30 ml of
heptane, and 10.9 g (0.1 mol) of ethyl diazoacetate (I)
was added. The mixture was heated for 7 h at 75 C,
and the solvent was distilled off. By fractional crys-
tallization of the residue from alcohol we isolated
5.75 g (36%) of compound IIIa and 1.2 g (8%) of
ethyl 3-benzoyl-4-phenyl-4,5-dihydro-1H-pyrazole-
5-carboxylate (IVa).
Thermolysis of ethyl 5-benzoyl-4-(3-bromo-
phenyl)-4,5-dihydro-1H-pyrazole (IIId). Compound
IIId, 2 g, was heated for 75 min at 210 220 C. After
cooling, the resulting material was subjected to
column chromatography on Al2O3 using hexane ether,
(1:1, by volume) as eluent to isolate 0.3 g (16%) of
ethyl c-2-benzoyl-t-3-(3-bromophenyl)cyclopropane-
carboxylate (IXb), mp 94 C, and 0.15 g (9%) of
4-(3-bromophenyl)-6-phenyl-2H-2-pyranone (XIIb),
mp 119 C.
Ethyl 5-benzoyl-4-(4-methylphenyl)-4,5-dihydro-
1H-pyrazole-3-carboxylate (IIIb) was synthesized in
a similar way from 4.44 g (0.02 mol) of 3-(4-methyl-
phenyl)-1-phenylpropenone and 4.56 g (0.04 mol) of
ester I. Yield 3.2 g.
Ethyl 5-benzoyl-4-(4-methoxyphenyl)-4,5-di-
hydro-1H-pyrazole-3-carboxylate (IIIc) was syn-
thesized in a similar way from 1 g (4 mmol) of
3-(4-methoxyphenyl)-1-phenylpropenone (IIc) in
10 ml of toluene and 0.95 g (8.4 mmol) of ester I.
Recrystallization of the product gave 0.22 g of com-
pound IIIc.
The ratio of isomeric dihydropyrazoles III and
IV was determined from the H NMR spectra of the
reaction mixtures. Below are given compound no.,
chemical shifts of the 4-H and 5-H protons ( , ppm),
1
and III:IV isomer ratios: IIIa, 5.22, 4.48, IVa,
,
4.91, 5; IIIb, 5.19, 4.46, IVb, 4.38, 4.88, 4; IIIc,
5.17, 4.44, IVc, 4.36, 4.87, 2; IIId, 5.21, 4.46, IVd,
4.38, 4.88, 5; IIIe, 5.19, 4.47, IVe, 4.38, 4.89, 3;
IIIf, 5.49, 5.02, IVf, 4.46, 5.12, 3; IIIg, 5.18, 4.49,
IVg, 4.38, 4.94, 4; IIIh, 5.14, 4.40, IVh, 4.38, 4.86,
5; IIIi, 5.18, 4.42, IVi, , 4.85, 2.
REFERENCES
Pyrazoles IIIe IIIi were obtained in a similar way.
Ethyl 5-deutero-3-benzoyl-4-phenyl-4,5-dihydro-
1H-pyrazole-5-carboxylate (VI). 1,3-Diphenylpro-
penone, 10 g (48 mmol), was dissolved in 30 ml of
heptane, and 8.5 g (74 mmol) of ethyl diazoacetate-d
was added. The mixture was heated for 7 h at 75 C
and evaporated. By fractional crystallization from
alcohol we isolated 0.55 g (4%) of pyrazole VI,
mp 103 C, and 3.5 g (22%) of compound IIIa.
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dissolved in 30 ml of acetic acid, and 1 ml of bromine
was added. After 45 min, the mixture was poured into
100 ml of water, and the precipitate was filtered off
and recrystallized from ethanol. Yield 0.5 g (50%),
mp 98 C [4]. Following the same procedure, from 1 g
(3.1 mmol) of a mixture of dihydropyrazoles IVa and
Va, 0.76 g (76%) of compound VII was obtained.
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Thermolysis of ethyl 5-benzoyl-4-phenyl-4,5-di-
hydro-1H-pyrazole-3-carboxylate (IIIa). Compound
IIIa, 2 g, was heated for 75 min at 210 220 C. The
mixture was cooled, and the product was recrystal-
lized from alcohol. Yield of ethyl c-2-benzoyl-t-3-
phenylcyclopropanecarboxylate (IXa) 0.2 g (11%),
mp 86 C. The residue was subjected to column
chromatography on Al2O3 using hexane ether (1:1,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 11 2001