Synthesis of 1-methyl-, 4-nitro-, 4-amino- and 4-iodo-1,2-dihydro-3H-pyrazol-3-ones

Article abstract of DOI:10.1002/jhet.5570380509

4-Aminopyrazole-3-ones 4b, e, f were prepared from pyrazole-3-ones 1b-d in a four-step reaction sequence. Reaction of the latter with methyl p-toluenesulfonate gave 1-methylpyrazol-3-ones 2b-d. Compounds 2b-d were treated with aqueous nitric acid to give 4-nitropyrazol-3-ones 3b-d. Reduction of compounds 3b-d by catalytic hydrogenation with Pd-C afforded the 4-amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole-3-ones derivatives 2c, d were reduced into aminopyrazole-3-ones 5e, f. 4-Iodopyrazole-3-ones 7a, 7c and 8 were prepared from the corresponding pyrazol-3-ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.

Full text of DOI:10.1002/jhet.5570380509

Sep-Oct 2001
Synthesis of 1-methyl-, 4-nitro-, 4-amino-
1065
and 4-iodo-1,2-dihydro-3H-pyrazol-3-ones
*
Y. C. Fiamegos, G. A. Pilidis and G. Varvounis
Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece
Received April 24, 2001
4-Aminopyrazole-3-ones 4b, e, f were prepared from pyrazole-3-ones 1b-d in a four-step reaction
sequence. Reaction of the latter with methyl p-toluenesulfonate gave 1-methylpyrazol-3-ones 2b-d.
Compounds 2b-d were treated with aqueous nitric acid to give 4-nitropyrazol-3-ones 3b-d. Reduction of
compounds 3b-d by catalytic hydrogenation with Pd-C afforded the 4-amino compounds 4b, e, f. Using
similar reaction conditions, nitropyrazole-3-ones derivatives 2c, d were reduced into aminopyrazole-3-ones
5e, f. 4-Iodopyrazole-3-ones 7a, 7c and 8 were prepared from the corresponding pyrazol-3-ones 2a, 2c and 6
and iodine monochloride or sodium azide and iodine monochloride.
J. Heterocyclic Chem. 38, 1065 (2001).
Pyrazol-3-ones are versatile compounds [1] that have
4b, e and f in 82, 77 and 78% yield. In a similar manner,
nitro derivatives 2c and 2d were reduced to amines 5e and
5f in 87 and 88% yield, respectively.
found application as intermediates and products in analy-
tical [2], agricultural [3], biological [4] and pharmaceutical
chemistry [5]. The use of 4-aminopyrazol-3-one deriva-
tives as chromogenic agents for the spectrophotometric
determination of phenols has been published recently [6].
We now report the synthesis of these derivatives.
The most common synthesis of 1,2-dihydro-3H-pyrazol-
3-ones is Knorr's reaction between a β-keto ester and
hydrazine hydrate or a mono or disubstituted hydrazine
[7-10]. The substituents on the ester and the hydrazine
have been greatly varied. All types of alkyl, alicyclic,
aralkyl and heterocyclic substituted esters have been used.
A large variety of monosubstituted alkyl, aryl and hetero-
cyclic hydrazines have been successfully employed [1].
Alkylation of pyrazole-3-ones at position 1 has been
carried out by alkyl halides [11], dialkyl sulfates [12]
diazomethane [13] and alkyl p-toluenesulfonates [14]. The
reaction of pyrazole-3-ones with alkyl p-toluenesulfonates
at 160° has generally given the highest yields of alkylated
products. Pyrazol-3-ones 1a-d reacted smoothly with
methyl p-toluenesulfonate to give 1-methylpyrazol-3-ones
2a [15,16] and 2b-d in excellent yields.
A well-established route for the introduction of an
amino group at position 4 of a pyrazol-3-one is first
selective nitration at this position and then reduction of the
resulting 4-nitro adduct. Two nitrating methods, 50%
aqueous nitric acid [17] and acetic anhydride in fuming
nitric acid [18], have been employed. The former
conditions give much higher yields and therefore pyrazole-
3-ones 2b-d were treated with 55% aqueous nitric acid at
0 to 80° to give the corresponding 4-nitro derivatives 3b-d
in 80, 78 and 70% yield.
1
1
1
a, R = H, R = Ph, b, R = H, R = 4-ClC H , c, R = H, R = 4-NO C H ,
6
4
2 6 4
1
1
1
d, R = NO , R = Ph, e, R = H, R = 4-NH C H , f, R = NH , R = Ph. (i)
methyl p-toluenesulfonate, (ii) 55% aq. HNO , 0-22°, (iii) H , 10% Pd-C.
2
2
6
4
2
3
2
A literature survey revealed that, by far, the most
reliable method to reduce nitropyrazole-3-ones is catalytic
hydrogenation. Although a large variety of catalysts have
been used, the best yields have been obtained with 10%
Pd-C [19]. Thus 4-nitropyrazol-3-ones 3b-d were reduced
smoothly by hydrogenation at 3 atmospheres and in the
presence of 10% Pd-C to afford the corresponding amines
In order to establish a more selective method for the
synthesis of 4-aminopyrazol-3-ones, a route via 4-halo-
pyrazol-3-ones was investigated. For example, substitution
of the halogen atom from 4-halopyrazol-3-ones by sodium
azide in the Gabriel reaction would afford the corres-
ponding 4-azidopyrazol-3-ones. Reaction of the latter with
tri-n-butylphosphine and then hydrolysis of the

1066
Y. C. Fiamegos, G. A. Pilidis and G. Varvounis
Vol. 38
intermediate iminophosphoranes would selectively yield
4-aminopyrazol-3-ones. For this purpose we selected to
synthesize 4-iodopyrazol-3-ones. Halogenation at position
4 of a pyrazol-3-one may be accomplished by a variety of
reagents. The products are mono- or dihalogeno
derivatives, which are versatile compounds that can
provide a further avenue for structural elaboration. In the
literature there are fewer 4-iodopyrazol-3-ones than the
other halogeno derivatives. Direct iodination [20] of a
4-unsubstituted pyrazole-3-one and replacement of a
4-chloromercuri group [21] with elemental iodine were the
first two methods that gave fairly good yields of 4-iodo-
pyrazol-3-ones. More recently it was demonstrated that
1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one
(antipyrine) was iodinated with bis(pyridine)iodonium(I)
tetrafluoroborate to give 4-iodoantipyrine in almost
quantitative yield [22].
any attempts to substitute iodine anion by azide anion in
these compounds failed giving back unreacted starting
material.
Alternatively, the synthesis 4-azidopyrazol-3-ones
directly from compounds 2a, 2c or 6, by a method
similar to that used for the preparation of α-azidovinyl-
ketones, was investigated. This work has been carried
out by Hassner and co-workers [25] who reported the
trans addition of iodine azide, prepared in situ by the
reaction of sodium azide and iodine monochloride, to a
variety of unsaturated systems. Thus α,β-unsaturated
ketones and esters were postulated to give intermediate
iodo azide adducts where iodine anion is substituted by
excess azide anion to afford diazido intermediates.
Trans elimination of hydrazoic acid from the diazido
adducts is reported to give unsaturated α -azides.
However upon reaction of compounds 2a, 2c or 6 with
sodium azide and iodine monochloride the corres-
ponding 4-iodo compounds 7a, 7c and 8 were obtained
in 45, 38 and 44% yield, respectively. A plausible
We now report that iodination of 2a, 2c or 6 [23] with
iodine monochloride [24] gave the corresponding 4-iodo
derivatives 7a, 7c and 8 in 70, 55 and 75% yield. However

Sep-Oct 2001
Synthesis of 1-methyl-, 4-nitro-, 4-amino- and 4-iodo-1,2-dihydro-3H-pyrazol-3-ones
1067
1-Methyl-5-(4-nitrophenyl)- 2-phenyl-1,2-dihydro-3H-pyrazol-
3-one (2c).
explanation for this result is that after the addition of in
situ generated iodine azide to 2a, 2c or 6, hydrazoic acid
elimination from the intermediate iodo azide adducts
occurred faster than substitution of iodine anion by
azide anion.
This compound was obtained as light-brown crystals
-1
1
(isopropyl alcohol/ether), mp 182-183°; ir: CO 1670 cm ; H
nmr: δ 2.95 (s, 3H, CH ), 5.88 (s, 1H, 4-H), 7.26-7.49 (m, 5H,
3
At present we are continuing our studies towards the
selective introduction of an amino group at position 4 of
1,2-dihydro-3H-pyrazol-3-ones.
phenyl protons), 7.69 (d, 2H, nitrophenyl β-protons, J = 9.1 Hz),
8.30 ppm (d, 2H, nitrophenyl α-protons, J = 9.1 Hz); APCI(-)ms:
m/z 295 (30), 294 (100); APCI(-) ms-ms (295): m/z .272 (60),
255 (50), 185 (10), 99 (20).
Anal. Calcd. for C H N O : C, 65.08; H, 4.44; N, 14.23.
Found: C, 65.09; H, 4.57; N, 14.10.
16 13
3 3
EXPERIMENTAL
1-Methyl-2-(4-nitrophenyl)- 5-phenyl-1,2-dihydro-3H-pyrazol-
3-one (2d).
Melting points were taken on a Büchi 510 apparatus and are
uncorrected. Infrared spectra were recorded on a Perkin-Elmer
783-B spectrometer solids were taken as Nujol mulls between
sodium chloride discs. Elemental analyses were performed on
a Carlo Erba 1106 elemental analyzer. Nuclear magnetic
resonance spectra were measured at 400 MHz on a Brüker
AMX 400 spectrometer using tetramethylsilane as internal
standard. Purity verification and mass spectra were obtained
This compound was obtained as light-brown crystals (ethyl
-1
1
acetate/methanol), mp 191-193°; ir: CO 1670 cm ; H nmr: δ
2.97 (s, 3H, CH ), 5.81 (s, 1H, 4-H), 7.47-7.54 (m, 5H, phenyl
3
protons), 7.73 (d, 2H, nitrophenyl β-protons, J = 9.1 Hz), 8.30
ppm (d, 2H, nitrophenyl α-protons, J = 9.1 Hz); APCI(-)ms: m/z
295 (20), 294 (100); APCI(-) ms-ms (295): m/z 280 (90), 265
(60), 170 (50).
by (i) an HPLC Waters system, type 616 with a Nova-Pak C
,
18
4 µm (3.9 mm x 15 cm, Waters 36975) column at 25° with ms
detector (Waters Integrity System, Milford MA). The ioniza-
tion was made at 70 eV, the source was at 230° and the
temperature of the PB (Particle Beam) interface set at 88° and
(ii) a Thermo Separation gradient pump HPLC system, with
Supelco, Supelcosil LC-18-DB, 3 µm (2.1 mm x 25 cm) at 25°
with an APCI (Atmospheric Pressure Chemical Ionization)
Finnigan MAT LCQ ion trap mass spectrometer. The ioniza-
tion was made in APCI temperature of 450° with the corona
discharge at -5.5 kV negative ionization (NI). Ms-ms spectra
of the corresponding molecular ions are also collected.
Anal. Calcd. for C H N O : C, 65.08; H, 4.44; N, 14.23.
Found: C, 65.10; H, 4.67; N, 14.05.
16 13
3 3
General Procedure for the Nitration of Pyrazol-3-ones 2b-d with
Nitric acid.
To a stirred solution of 55% aqueous nitric acid (4 ml) at 0°
was added portion-wise the appropriate pyrazole-3-one 2b-d
(4.8 mmoles). After the addition was complete the temperature of
the reaction mixture was raised to 70° and then stirring was
continued at that temperature for 6 hours. After cooling the
reaction mixture was poured onto ice (50 g) and the resulting
precipitate filtered, washed with water and crystallized from an
appropriate solvent to give 4-nitropyrazole-3-ones 3b-d in 80, 78
and 70% yield, respectively.
Analytical TLC was carried out on Fluka silica gel 60 F
.
254
Solvents and reagents were of analytical grade and were used
as received from the manufacturers.
General Procedure for the Methylation of Pyrazol-3-ones 1b-d
with Methyl p-Toluenesulfonate.
5-(4-Chlorophenyl)-1-methyl-4-nitro-2-phenyl-1,2-dihydro-3H-
pyrazol-3-one (3b).
A stirred mixture of the appropriate of pyrazole-3-one 1b-d
(30 mmoles) and methyl p-toluenesulfonate (50 mmoles) was
heated at 130-160° for 6-7 hours. The temperature of the reaction
mixture was lowered to 80°, water (20 ml) added and then left
stirring at that temperature for 20 minutes. The reaction mixture
was cooled to room temperature and then brought to pH 8-9 by
the addition of 40% aqueous sodium hydroxide. The crude
precipitate was filtered off, washed with water and crystallized
from an appropriate solvent to give 1-methylpyrazole-3-ones
2b-d in 78, 70 and 83% yield, respectively.
This compound was obtained as light brown crystals
(isopropyl alcohol/petroleum ether bp 40-60°), mp 86-89°; ir: CO
-1
1
1670 cm ; H nmr: δ 3.14 (s, 3H, CH ), 7.36-7.50 (m, 9H,
3
phenyl and nitrophenyl protons); APCI(-) ms: m/z 330 (100), 328
(45); APCI(-) ms-ms (328): m/z .298 (80), 285 (50), 243 (15),
196 (30).
Anal. Calcd. for C H ClN O : C, 58.28; H, 3.67; N, 12.74.
16 12
3 3
Found: C, 58.35; H, 3.79; N, 12.38.
1-Methyl-4-nitro-5-(4-nitrophenyl)- 2-phenyl-1,2-dihydro-3H-
pyrazol-3-one (3c).
5-(4-Chlorophenyl)-1-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-
3-one (2b).
This compound was obtained as orange-red crystals
(methanol/isopropyl alcohol), mp >260°; ir: CO 1670, NO 1525,
2
-1
1
This compound was obtained as yellow crystals (isopropyl
1510 cm ; H nmr (DMSO-d ): δ 3.17 (s, 3H, CH ), 7.56-7.65
6
3
-1 1
alcohol), mp 167-168°; ir: CO 1670 cm ; H nmr: δ 3.19 (s, 3H,
(m, 5H, phenyl protons), 7.8 (d, 2H, nitrophenyl α-protons,
J = 8.9), 8.45 ppm (d, 2H, nitrophenyl α-protons, J = 8.9);
APCI(-)ms: m/z 340 (100), 339 (45); APCI(-) ms-ms (340): m/z
.279 (35), 250 (30), 185 (50), 117 (35), 99 (10).
CH ), 5.79 (s, H, 4-H), 7.22-7.69 ppm (m, 9H, benzene protons);
3
APCI(-)ms: m/z 285(100), 283(50); APCI(-) ms-ms (283): m/z
263 (40), 243 (15), 196 (30).
Anal. Calcd. for C H ClN O: C, 67.49; H, 4.60; N, 9.84.
Anal. Calcd. for C H N O : C, 56.47; H, 3.55; N. 16.46.
16 13
2
16 12
4 5
Found: C, 67.57; H, 4.78; N, 9.65.
Found: C, 56.55; H, 3.87; N, 16.29.

1068
Y. C. Fiamegos, G. A. Pilidis and G. Varvounis
Vol. 38
1-Methyl-4-nitro-2-(4-nitrophenyl)- 5-phenyl-1,2-dihydro-3H-
pyrazol-3-one 3d.
5-(4-Aminophenyl)-1-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-
3-one (5e).
This compound was obtained as orange-red crystals
This compound was obtained as colorless crystals
-1 1
(methanol), mp 230-232°; ir: CO 1670, NO 1525, 1515 cm ; H
(methanol/diethyl ether), mp 154-155.5°; ir: NH 3320, 3220,
2
2
-1
1
nmr: δ 3.18 (s, 3H, CH ), 7.47-7.59 (m, 5H, phenyl protons),
CO 1670 cm ; H nmr: δ 2.86 (s, 3H, CH ), 3.85 (s, 2H, NH ),
3 2
3
7.61 (d, 2H, nitrophenyl β-protons, J = 8.9), 8.36 ppm (d, 2H,
nitrophenyl α-protons, J = 8.9); APCI(-)ms: m/z 340 (100), 339
(60); APCI(-) ms-ms (340): m/z 311 (40), 265 (60), 235 (90), 201
(60), 171 (30), 134 (25).
5.55 (s, 1H, 4- H), 7.11-7.42 (m, 5H, phenyl protons), 6.61
(d, 2H, benzene α-protons, J = 8.5), 7.21 (d, 2H, benzene
β
-
protons, J = 8.5); APCI(-)ms: m/z 265 (40), 264 (100), PB(EI)
ms: m/z 265 (100), 250 (25), 222 (20), 173 (35), 117 (45).
Anal. Calcd. for C H N O: C, 72.43; H, 5.70; N. 15.84.
Anal. Calcd. for C H N O : C, 56.47; H, 3.55; N. 16.46.
16 12
4
5
16 15 3
Found: C, 56.62; H, 3.79; N, 16.31.
Found: C, 72.65; H, 5.63; N, 15.52.
General Procedure for the Reduction of Nitropyrazol-3-ones 2c,d
and 3b-d.
2-(4-Aminophenyl)-1-methyl-5-phenyl-1,2-dihydro-3H-pyrazol-
3-one (5f).
A solution of 4-nitropyrazol-3-ones 3b-d (6 mmoles) in
methanol (150 ml) was hydrogenated at 3 atmospheres for
24 hours over 10% palladium-on-charcoal (0.2 g). After removal
of the catalyst by filtration, evaporation of methanol in vacuo
gave a residue. Crystallization of the residue from an appropriate
solvent gave 4b,e,f and 5e,f in 82, 77, 86, 88 and 87% yield,
respectively.
This compound was obtained as colorless crystals (ethyl
acetate/petroleum ether bp 40-60°), mp 129-130°; ir: NH
2
-1
1
3370, 3220, CO 1670 cm ; H nmr: δ 2.92 (s, 3H, CH ), 3.72
3
(s, 2H, NH ), 5.71 (s, 1H, 4-H), 6.70 (d, 2H, benzene
2
α-protons, J = 8.6), 7.21 (d, 2H, benzene β-protons, J = 8.6),
7.41-7.45 ppm (m, 5H, phenyl protons); APCI(-) ms: m/z 265
(90), 264 (30), 263 (100), PB(EI) ms: m/z 265 (100), 236 (95),
222 (10), 195 (20), 160 (15), 118 (90), 108 (30), 92 (20), 79
(25), 65 (25).
4-Amino-5-(4-chlorophenyl)-1-methyl-2-phenyl-1,2-dihydro-
3H-pyrazol-3-one (4b).
Anal. Calcd. for C H N O: C, 72.43; H, 5.70; N. 15.84.
16 15
3
This compound was obtained as off-yellow needles
Found: C, 72.56; H, 5.99; N, 15.57.
(methanol/diethyl ether), mp 86-89°; ir: NH 3420, 3360, CO
2
General Procedure for the Iodination Pyrazol-3-ones 2a,c and 6
Iodine monochloride.
-1
1
1670 cm ; H nmr: δ 2.91 (s, 3H, CH ), 3.36 (s, 2H, NH ),
3
2
7.40-7.67 ppm (m, 9H, p-chlorophenyl and phenyl protons);
APCI(-)ms: m/z 299 (25), 298 (100); APCI(-) ms-ms (299): m/z
298 (50), 285 (50), 263 (30), 243 (15).
To a stirred and cooled (0°) solution of pyrazol-3-one 2a [16],
2c or 6 (0.80 mmoles) in acetonitrile (5 ml), iodine mono-
chloride (1.1 mmoles) was added portionwise. The temperature
was allowed to reach room temperature and then stirring was
continued for 18 hours. The reaction mixture is poured into cold
water (50 ml) and extracted with chloroform (3 x 15 ml). The
combined organic layers were treated with a 5% aqueous
solution of sodium hydrogen sulfide, the organic layer separated
Anal. Calcd. for C H ClN O: C, 64.11; H, 4.71; N. 14.02.
16 14
3
Found: C, 64.28; H, 4.79; N, 13.81.
4-Amino-1-methyl-5-(4-aminophenyl)- 2-phenyl-1,2-dihydro-
3H-pyrazol-3-one (4e).
This compound was obtained as colorless crystals (chloro-
form/petroleum ether bp 40-60°), mp 148-150°; ir: NH 3390,
and dried (Na SO ). The solvent was removed under reduced
2
2 4
-1
1
3320, 3220, CO 1670 cm ; H nmr: δ 2.68 (s, 3H, CH ), 3.42
pressure to give a residue. The residue was crystallized from an
appropriate solvent to give 7a,c and 8 in 75, 55 and 75% yield,
respectively.
3
(s, 2H, 4-NH ), 5.23 (s, 2H, p-NH C H ), 6.72 (d, 2H, benzene
2
2 6 4
α-protons, J = 8.3), 7.56 (d, 2H, benzene β-protons, J = 8.36),
7.15-7.41 ppm (m, 5H, phenyl protons); APCI(-)ms: m/z 280
(15), 279 (100); APCI(-) ms-ms (280): m/z 255 (40), 185 (5),
99 (20). PB(EI) ms: m/z 280 (60), 160 (30), 133 (70), 120
(100).
4-Iodo-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (7a).
This compound was obtained as colorless needles (chloro-
form/petroleum ether bp 40-60°), mp 176-178°; ir: CO 1670
-1
1
Anal. Calcd. for C H N O: C, 68.55; H, 5.75; N. 19.99.
cm ; H nmr: δ 2.91 (s, 3H, CH ), 7.25-7.49 ppm (m, 10H,
16 16
4
3
Found: C, 68.69; H, 5.83; N, 19.74.
phenyl protons); PB(EI) ms: m/z 376 (75), 284 (20), 178 (25),
129 (90), 118 (80), 105 (30), 91 (55), 77 (95) 63 (40), 51 (100).
4-Amino-1-methyl-2-(4-aminophenyl)- 5-phenyl-1,2-dihydro-
3H-pyrazol-3-one (4f).
Anal. Calcd. for C
H IN O: C, 51.08; H, 3.48; N. 7.45.
16 13 2
Found: C, 51.11; H, 3.65; N, 7.13.
This compound was obtained as colorless needles (ethyl
4-Iodo-1-methyl-5-(4-nitrophenyl)-2-phenyl-1,2-dihydro-3H-
pyrazol-3-one (7c).
acetate/petroleum ether bp 40-60°), mp 175-178°; ir: NH 3390,
2
-1
1
3340, 3220, CO 1670 cm ; H nmr: δ 2.64 (s, 3H, CH ), 3.51
3
(s, br, 4H, 4-NH and NH C H ), 6.69 (d, 2H, benzene
This compound was obtained as colorless needles (chloro-
form/diethyl ether), mp 133-135°; ir: CO 1670 cm ; H nmr: δ
2
2
6
4
-1
1
α-protons, J = 8.6), 7.28 (d, 2H, benzene β-protons, J = 8.6),
7.27-7.50 ppm (m, 5H, phenyl protons); APCI(-)ms: m/z
280(10), 279(100); APCI(-) ms-ms (280): m/z 279(85),
265(100), 171(40).
2.94 (s, 3H, CH ), 7.28-7.50 (m, 5H, phenyl protons), 7.69
3
(d, 2H, benzene β-protons, J = 8.7), 8.31 ppm (d, 2H, benzene
α-protons, J = 8.7); APCI(-) ms: m/z 420 (100), 419 (30).
Anal. Calcd. for C H N O: C, 68.55; H, 5.75; N. 19.99.
Anal. Calcd. for C H IN O : C, 45.63; H, 2.87; N. 9.98.
16 16
4
16 12 3 3
Found: C, 68.59; H, 5.79; N, 19.89.
Found: C, 45.66; H, 3.09; N, 9.72.

Sep-Oct 2001
Synthesis of 1-methyl-, 4-nitro-, 4-amino- and 4-iodo-1,2-dihydro-3H-pyrazol-3-ones
1069
[5] A. M. Farghaly, I. Chaaban, M. A. Khalil and A. A. Bekhit,
Arch. Pharm (Weinheim, Ger.) 323, 833 (1990).
[6] Y. C Fiamegos, C. D. Stalikas, G. A. Pilidis and M. I.
Karayannis, Anal. Chim. Acta, 403, 315 (2000).
4-Iodo-5-methyl-1,2-diphenyl-1,2-dihydro-3H-pyrazol-3-one (8).
This compound was obtained as colorless needles
-1
1
(ethanol/water), mp 114.5-116°; ir: CO 1670 cm ; H nmr: δ
2.10 (s, 3H, CH ), 6.92-7.27 (m, 10H, phenyl protons); PB(EI)
3
[7] L. Knorr, Chem. Ber., 16, 2597 (1883).
ms: m/z 376 (65), 219 (50), 178 (35), 130 (60), 101 (80), 89 (70),
75 (100).
˘
[8] J. Cierník and A. Mistr, Collect. Czech. Chem. Commun., 31,
4669 (1966).
Anal. Calcd. for C
Found: C, 51.19; H, 3.69; N, 7.35.
H IN O: C, 51.08; H, 3.48; N. 7.45.
[9] N. V. Khromov-Borisov, Zhur. Obshchei Khim., 25, 136
(1955); Chem. Abstr., 8257i (1955).
16 13 2
General Procedure for the Treatment of Pyrazol-3-ones 2a,c
and 6 with Sodium azide and Iodine monochloride.
To a stirred and cooled (0°) solution of pyrazol-3-one 2a,c or 6
(1 mmole) in acetonitrile (5 ml), sodium azide (2.5 mmoles) and
iodine monochloride (1.1 mmoles) were added portionwise.
(Caution! Explosions have been reported on evaporation of
solutions of iodine azide to dryness. Mixtures containing
unreacted iodine azide should be washed with sodium bisulfite).
The work-up that followed was similar to the previous General
Procedure and gave 7a,c and 8 in 45, 38 and 44% yield,
respectively. Compounds 7a,c and 8 were in all respects identical
to authentic samples.
[10] R. Kitamura, J. Pharm. Soc. Jap., 61, 19 (1941).
[11] C. A. Rojahn, Chem. Ber. 55, 190 (1922).
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Acknowledgements
The authors wish to thank the General Secretariat of Research
and Technology, Athens for financial support (PAVE grant no.
92BE121) and Dr. A. Troganis for NMR spectra measured on a
Brüker AMX 400 spectrometer financed by the University of
Ioannina.
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