Synthesis and NMR-Spectroscopic Investigations with 4-Chloroacyl-1-phenylpyrazolin-5-ones

Article abstract of DOI:10.1002/jhet.3015

The synthesis of various 4-acylpyrazolones bearing in the acyl moiety either a terminal chloro-substituent or a terminal ortho-chlorophenyl group was achieved by reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one (tautomer to 3-methyl-1-phenyl-1H-pyrazol-5-ol) with the corresponding acid chloride using calcium hydroxide / 1,4-dioxane. In one case (reaction with chlorobutanoyl chloride) a spontaneous cyclization occurred leading to the corresponding oxepino[2,3-c]pyrazole. Detailed NMR spectroscopic investigations with all prepared compounds were performed.

Full text of DOI:10.1002/jhet.3015

Month 2017
Synthesis and NMR-Spectroscopic Investigations with
4-Chloroacyl-1-phenylpyrazolin-5-ones
Gernot A. Eller* and Wolfgang Holzer*
Department of Pharmaceutical Chemistry, Division of Drug Synthesis, University of Vienna, Althanstrasse 14, A-1090
Vienna, Austria
*
E-mail: gernot.eller@univie.ac.at; wolfgang.holzer@univie.ac.at
Received May 27, 2017
DOI 10.1002/jhet.3015
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
O
Me
Me
1
step
R
a
b
c
d
R = −CH Cl
2
N
N
OH
N
R = −CH CH Cl
N
OH
2
2
Ph
Ph
R = −CH
2
CH
2
CH
2
Cl [not isolated]
R = −CH CH CH CH Cl
2
2
2
2
1
3
e
f
R =
R =
R =
O
O
Cl
Me
Me
N
Cl
N
Cl
Cl
N
OH
N
O
Ph
Ph
g
3
c
4
[
not isolated]
The synthesis of various 4-acylpyrazolones bearing in the acyl moiety either a terminal chloro-substituent
or a terminal ortho-chlorophenyl group was achieved by reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one
(
tautomer to 3-methyl-1-phenyl-1H-pyrazol-5-ol) with the corresponding acid chloride using calcium
hydroxide / 1,4-dioxane. In one case (reaction with chlorobutanoyl chloride) a spontaneous cyclization
occurred leading to the corresponding oxepino[2,3-c]pyrazole. Detailed NMR spectroscopic investigations
with all prepared compounds were performed.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
RESULTS AND DISCUSSION
During the last years, we investigated the C-4 acylation
of pyrazolones (5-hydroxypyrazoles) with different acid
chlorides (carbonyl chlorides) under the typical
conditions (calcium hydroxide / 1,4-dioxane) initially
described by Skytte Jensen in the 1950s [1–6].
Depending on the nature of the acid chloride, the
obtained 4-acylpyrazolones were transformed into a
huge number of hitherto unknown fused pyrazole
ring systems [7–14]. One simple and smart synthetic
strategy is based on the use of ortho-halogenated
aromatic carboxylic acid chlorides in the acylation
reaction to finally achieve the correspondingly fused
pyrano[2,3-c]pyrazolones. While with less reactive
aromatic acid chlorides (e.g., 2-chlorobenzoyl chloride
The reaction of the commercially available pyrazolone
with the corresponding chloroacetyl chloride,
1
chloropropanoyl chloride, and chloropentanoyl chloride,
in the acylation reaction (calcium hydroxide / 1,4-
dioxane) gave the expected 4-(chloroacetyl)pyrazole 3a,
4-(chloropropanoyl)pyrazole 3b, and 4-(chloropentanoyl)
pyrazole 3d, respectively (Scheme 2).
However, it should be noted that we were able to
isolate and unambiguously elucidate an interesting
dimeric side-product 5 in small quantities upon reaction
of 1 with chloroacetyl chloride (Scheme 3), which had
not been reported in previous preparations of 3a [1,15,16].
We explained the unusually low yield for the propanoyl
derivative 3b with the rather unstable nature of the
compound. It showed a tendency to polymerize during
[9], “Path A”), a second synthetic step for the
intramolecular cyclization reaction is needed to access the
annellated systems (NaH/DMF), the acylation reaction of
more reactive acid chlorides (e.g., 2-chloronicotinoyl
chloride [8], “Path B”) immediately yields the
corresponding fused ring system (Scheme 1).
the reaction and workup. Hence
–
although
a
theoretically perfect intermediate (from a steric point of
view) for intramolecular cyclization – we were not able
to transform it to the corresponding pyrano[2,3-c]
pyrazole ring system.
In this paper, we present the results of the acylation
reaction of 1 with several chlorinated aliphatic acid
chlorides.
Interestingly, upon reaction of pyrazolone 1 with the
homologue chlorobutanoyl chloride, the expected
4-(chlorobutanoyl)pyrazole 3c was not isolated, instead
©
2017 Wiley Periodicals, Inc.

G. A. Eller and W. Holzer
Vol 000
Scheme 1. (a) o-Haloarenecarbonyl chloride, Ca(OH)
2
, 1,4-dioxane; (b) NaH, DMF.
O
O
Me
Me
Me
(a)
(
a)
activ.
het.)-
arom.
(het.)-
(
arom
N
N
N
Path B
N
O
N
OH
N
O
Ph
Ph
Ph
1
Path A (a)
(b)
O
Me
inact.
(
het.)-
N
arom.
N
O
H
Cl(Br)
Ph
Scheme 2. Synthesis of the title compounds.
O
Me
acid chloride
2)
Me
(
R
a
b
c
d
R = −CH Cl
N
2
N
OH
N
Ca(OH)2
N
OH
R = −CH
2
CH
2
Cl
Ph
1,4-dioxane
R = −CH CH CH Cl [not isolated]
2 2 2
Ph
R = −CH CH CH CH Cl
2
2
2
2
1
3
e
f
R =
R =
R =
O
O
Cl
Me
Me
N
Cl
N
Cl
Cl
N
OH
N
O
Ph
Ph
g
3
c
4
[
not isolated]
Scheme 3. Formation of the dimeric by-product 5 in the course of the synthesis of 3a.
O
Cl
Cl
O
O
Me
Me
Cl
Me
Me
(
2a)
N
+
N
OH
N
N
N
Ca(OH)2
,4-dioxane
N
OH
N
O
H
O
H
N
Ph
1
Ph
Ph
Ph
1
3a
5
byproduct (<3%)
the hitherto almost unknown oxepino[2,3-c]pyrazole ring
system 4 was obtained in good yield (83%). Obviously,
under the applied reaction conditions, a spontaneous
cyclization did occur (Scheme 2).
high yield (Scheme 2). Any attempts to cyclize these
compounds under usual conditions (NaH/DMF, reflux)
did fail.
NMR spectroscopic investigations.
The prototropic
Additionally, we reacted pyrazolone 1 with three
homologue ortho-chlorobenzoyl chlorides: (o-chlorophenyl)
acetyl chloride, o-chlorohydrocinnamoyl chloride, and
o-chlorocinnamoyl chloride. In each case, the corres-
ponding 4-acylpyrazole 3e, 3f, and 3g, was obtained in
tautomerism of pyrazolones and thus also of
4-acylpyrazolones has been extensively reviewed [3–
6,17,18]. The – in principle – possible tautomeric forms of
the latter are depicted in Scheme 4. In CDCl solution,
3
compounds of type
3
are mainly present in the
Scheme 4. Tautomeric forms of 4-acylpyrazolones.
2
2
2
2
2
2
R
R
R
R
R
R
HO
3
3
3
3
3
3
3
2
R
O
R
R
O
R
O
R
OH
R
R
R
O
O
H
H
N
N
N
N
N
N
N
OH
O
O
H
O
O
O
O
N
R
N
R
N
R
N
R
N
R
N
R
N
R
1
1
1
1
1
1
1
A
A'
B
C
D
D'
E
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and NMR-Spectroscopic Investigations with
4-Chloroacyl-1-phenylpyrazolin-5-ones
1
13
3 6
Scheme 5. Crucial H (in italics) and C NMR chemical shifts of 3 g in CDCl and DMSO-d solution.
Cl
Cl
Cl
7.93
8
.30
7.93
135.3
135.3
O
7.17
139.6
8
.05
121.8
Me
126.9
8
.05
126.9
Me
O
Me
O
NOE
other forms
HN
H
N
O
N
N
O
OH
N
N
3
g (CDCl3)
3g (DMSO-d6)
hydroxypyrazole form with an intramolecular hydrogen
bond between pyrazole-OH and the C = O oxygen atom
CONCLUSION
(
Scheme 4, form A’), what – amongst other things – is
The reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one
with various chlorinated carbonyl chlorides under
“Skytte-Jensen”-conditions (calcium hydroxide, 1,4-
dioxane) gave the corresponding 4-acylpyrazolones. In
one case (reaction with chlorobutanoyl chloride), the
initially formed 4-acylpyrazolone underwent intramo-
lecular cyclization to the respective oxepino[2,3-c]
pyrazole.
1
supported by the large H–NMR chemical shift of the OH
resonance (for instance 3d: 12.30 ppm).
However, with compound 3g – the reaction product
of 1 with 2-chlorocinnamoyl chloride – noticeable
phenomena were observed in the course of the NMR
investigations. Thus, large differences are observed
between spectra taken from CDCl solutions compared
3
with those recorded in DMSO-d6. In CDCl3,
predominant presence of the hydroxypyrazole tautomer
can be assumed, here the enone system of the
EXPERIMENTAL
4
-substituent shows the typical low-field shift of the
1
3
signal due to the proton and the
C
atom,
Instruments.
Melting points were determined on a
respectively, in beta position to the carbonyl moiety
Scheme 5, left). In contrast, the spectra in DMSO-d6
Reichert–Koflerhot-stage microscope and are uncorrected.
Mass spectra were obtained on a Shimadzu QP 1000
instrument (EI, 70 eV, MS) and on a Finnigan MAT 8230
instrument (EI, 70 eV, HRMS).
(
solution not only show a distinct dynamic behavior
that results in marked line broadening for the
proton and the carbon signals of the enone system,
but also for those of the pyrazole carbon atoms.
An additional, interesting observation is that here – in
contrast to CDCl3 solution, the difference between
COCH= (126.9 ppm) and COCH=CH (135.3 ppm) is
considerably smaller and COCH=CH (7.93 ppm) now
Elemental analyses were performed at the
Microanalytical Laboratory, University of Vienna,
1
13
Austria. The H and C NMR spectra were recorded on
Varian UnityPlus 300 spectrometer at 28°C
a
1
13
(299.95 MHz for H, 75.43 MHz for C), a Bruker Avance
500 spectrometer at 293 K (500.13 MHz for H,
125.77 MHz for C) or a Bruker Avance III 400 spectrom-
1
13
exhibits
a
smaller
chemical
shift
than
1
13
COCH= (8.05 ppm). A possible explanation for the
latter phenomenon is a non-ignorable contribution of
eter (400.23 MHz for H, 100.64 MHz for C). The center
of the solvent signal was used as an internal standard,
which was related to tetramethylsilane with δ 7.26 ppm
the NH-form, in which COCH= may receive
a
1
1
downfield shift due to an anisotropy effect caused by
the pyrazolone C=O moiety. This is supported by an
NOE between the acidic proton and the methyl
protons in the NOESY spectrum, which is only
explicable by the presence of the NH-form (form C
in Scheme 1) (or the exocyclic double bond form E).
Moreover, in the NOESY spectra, chemical exchange
between the two enone protons is observed, what
hints to a complex tautomeric equilibrium with the
involvement of several tautomeric forms. These
findings are in full agreement with results found for
closely related species [3,4].
( H in CDCl ), δ 2.49 ppm ( H in DMSO-d ), δ
3 6
13
13
77.0 ppm ( C in CDCl ), and δ 39.5 ppm ( C in
3
DMSO-d ). The digital resolutions were 0.2 Hz/data point
6
1
13
in the H NMR spectra and 0.4 Hz/data point in the
NMR spectra ( H broadband decoupling or gated
C
1
15
decoupling). N NMR spectra were obtained on a Bruker
Avance 500 (50.68 MHz) or Bruker Avance III 400 instru-
ment (40.55 MHz) with a “directly” detecting broadband
observation probe and were referenced against external
nitromethane. Systematic names were generated with
ACD/Name [19] according to current International Union
of Pure and Applied Chemistry recommendations and were
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G. A. Eller and W. Holzer
Vol 000
also checked manually to ensure the correct use of nomen-
clature within this publication [20]. Yields were not
optimized.
Ph’ H-2,6), 7.463 (2H, m, Ph’ H-3,5), 7.455 (2H, m, Ph
H-3,5), 7.30 (1H, m, Ph’ H-4), 7.27 (1H, m, Ph H-4),
3.74 (2H, s, CH ), 2.31 (3H, s, Me), 2.27 (3H, s Me’);
2
13
C NMR (125 MHz, DMSO-d ): δ 190.3 (CO), 159.5
General procedure for the synthesis of the title
6
compounds.
Under anhydrous conditions, a solution/
suspension of the corresponding chloro-alkanoyl chloride
a–g (10 mmol) in anhydrous 1,4-dioxane (5 mL) was
(Py C-5), 158.3 (Py’ C-5), 150.0 (Py C-3), 147.3 (Py’
C-3), 137.6 (Ph C-1), 135.9 (Ph’ C-1), 129.1 (Ph’ C-3,5),
128.9 (Ph C-3,5), 126.5 (Ph’ C-4), 125.8 (Ph C-4), 121.3
(Ph C-2,6), 121.2 (Ph’ C-2,6), 104.2 (Py C-4), 98.4 (Py’
2
added to a suspension of pyrazolone 1 (1.74 g, 10 mmol)
and Ca(OH)2 (1.46 g, 20 mmol) in anhydrous 1,4-
dioxane (5 mL). The reaction mixture was heated at
reflux under stirring for 2–3 h. After cooling to room
temperature, the mixture was acidified with 2 M
hydrochloric acid (20 mL), stirred for 30 min, and poured
into water (20 mL). After 30 min, solid products were
filtered off, washed with water, and recrystallized.
C-4), 33.4 (CH ), 15.2 (Me), 11.2 (Me’); ms (m/z, %):
2
+
388 (M , 50), 201 (60), 188 (26), 187 (100), 175 (55),
174 (29), 77 (69); hrms (EI): Calcd. for C H N O
2 20 4 3
2
+
([M] ): m/z 388.1535, found: m/z 388.1524. Anal. Calcd.
for C H N O ∙ 0.5 H O: C, 66.49; H, 5.33; N, 14.10.
2
2
20
4
3
2
Found: C, 66.28; H, 5.35; N, 13.97.
3
-Chloro-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)
propan-1-one (3b). This compound was obtained in 17%
2
-Chloro-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)
ethan-1-one (3a). This compound was obtained in 70%
yield as a yellowish powder (that was rather unstable due
to obvious polymerization); mp 92–95°C. H NMR
1
yield as an almost colorless powder; mp 76–80°C
1
(
(
(
aqueous methanol), (lit. [1] mp 88°C). H NMR
(500 MHz, CDCl
): δ 10.90 (1H, br s, OH), 7.79 (2H, m,
3
400 MHz, DMSO-d ): δ 7–14 (very br s, 1H, OH), 7.66
2H, m, Ph H-2,6), 7.47 (2H, m, Ph H-3,5), 7.28 (1H, m,
Ph H-4), 4.79 (2H, s, CH ), 2.43 (3H, s, Me); H NMR
Ph H-2,6), 7.43 (2H, m, Ph H-3,5), 7.28 (1H, m, Ph
6
3
H-4), 3.90 (2H, t, J = 6.6 Hz, CH Cl), 3.21 (2H, t,
2
1
3
13
J = 6.6 Hz, COCH
), 2.47 (3H, s, Me); C NMR
2
2
(
300 MHz, CDCl ): δ 9.95 (1H, br s, OH), 7.79 (2H, m,
(125 MHz, CDCl ): δ 193.8 (CO), 159.6 (pyrazole C-5),
3
3
Ph H-2,6), 7.45 (2H, m, Ph H-3,5), 7.31 (1H, m, Ph
147.4 (pyrazole C-3), 136.9 (Ph C-1), 129.1 (Ph C-3,5),
126.8 (Ph C-4), 120.8 (Ph C-2,6), 103.9 (pyrazole C-4),
1
3
H-4), 4.42 (2H, s, CH ), 2.50 (3H, s, Me); C NMR
2
(
100 MHz, DMSO-d ): δ 185.1 (CO), 160.4 (pyrazole
41.9 (COCH ), 38.2 (CH Cl), 15.7 (Me); ms (m/z, %):
266 (M , 12), 264 (M , 36), 229 (100), 228 (37), 201
2 2
+
6
+
C-5), 150.7 (pyrazole C-3), 136.0 (Ph C-1), 129.0 (Ph
C-3,5), 125.9 (Ph C-4), 120.6 (Ph C-2,6), 102.5 (pyrazole
(68), 91 (36), 77 (46); hrms (EI): Calcd. for
1
+
C-4), 48.1 (CH ,
J = 130.5 Hz); C NMR (75 MHz, CDCl ): δ 188.8 (CO,
J
=
151.5 Hz), 13.8 (Me,
C
H
13
13ClN
O
2
2
([M] ): m/z 264.0666. Found: m/z
2
1
2
13
264.0657.
3
3-Methyl-1-phenyl-6,7-dihydro-1H-oxepino[2,3-c]pyrazol-
J(CO,CH ) = 3.5 Hz), 159.7 (pyrazole C-5), 147.0
2
4
(5H)-one (4). This compound was obtained in 83% yield
(
(
(
pyrazole C-3), 136.8 (Ph C-1), 129.1 (Ph C-3,5), 127.1
as an off-white powder; mp 174–177°C (aqueous dioxane).
Ph C-4), 121.0 (Ph C-2,6), 102.1 (pyrazole C-4), 45.3
1
1
1
15
H NMR (300 MHz, CDCl ): δ 7.96 (2H, m, Ph H-2,6),
3
CH , J = 149.6 Hz), 15.4 (Me, J = 128.7 Hz);
N
2
7
.36 (2H, m, Ph H-3,5), 7.11 (1H, m, Ph H-4), 4.46 (2H,
NMR (40 MHz, DMSO-d ): δ À203.6 (N-1), N-2 was
6
3
3
15
t, J = 7.2 Hz, OCH CH ), 3.38 (2H, t, J = 7.9 Hz,
2 2
not found; N NMR (50 MHz, CDCl ): δ À102.1
3
+
+
COCH ), 2.33 (3H, s, Me), 2.18 (2H, m, CH CH CH );
2 2 2 2
(
3
N-2), À190.0 (N-1); ms (m/z, %): 252 (M , 9), 250 (M ,
1
3
C NMR (75 MHz, CDCl ): δ 179.3 (C-4), 165.8
3
0), 201 (100), 77 (49). Anal. Calcd. for C H ClN O : C,
12 11 2 2
2
(C-8a), 147.8 (C-3, J(C3,Me) = 7.4 Hz), 139.0 (Ph C-1),
5
7.49; H, 4.42; N, 11.17. Found: C, 57.34; H, 4.49; N, 11.22.
1
28.5 (Ph C-3,5), 124.0 (Ph C-4), 118.6 (Ph C-2,6),
1
,2-Bis(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)ethan-
1
1
-one (5). Once upon a reaction of pyrazolone 1 with
103.4 (C-3a), 75.2 (C-7, J = 152.4 Hz), 31.2 (C-5,
1
1
1
J = 136.8 Hz), 22.4 (C-6, J = 135.1 Hz), 16.4 (Me,
J = 128.9 Hz); N NMR (50 MHz, CDCl ): δ À87.2
chloroacetyl chloride (2a), a small amount (< 3%) of a
slightly beige powder was isolated and unambiguously
identified as the dimer 5.
15
3
+
(N-2), À189.7 (N-1); ms (m/z, %): 242 (M , 100), 201
(32), 200 (19), 91 (41), 77 (22), 67 (28). Anal. Calcd. for
C H N O : C, 69.41; H, 5.82; N, 11.56. Found: C,
14 14 2 2
6
9.22; H, 5.89; N, 11.60.
5
-Chloro-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)
pentan-1-one (3d). This compound was obtained in 83%
yield as a beige powder; mp 95–97°C (aqueous dioxane).
1
H NMR (500 MHz, CDCl ): δ 12.30 (1H, s, OH), 7.81
3
(2H, m, Ph H-2,6), 7.44 (2H, m, Ph H-3,5), 7.28 (1H, m,
Ph H-4), 3.59 (2H, m, ClCH ), 2.78 (2H, m, COCH ),
2.47 (3H, s, Me), 1.90 (4H, m, COCH CH CH ); H
2 2 2
2
2
1
1
Mp 256–259°C. H NMR (500 MHz, DMSO-d ): δ 10.7
6
(2H, br s, OH, OH’), 7.75 (2H, m, Ph H-2,6), 7.64 (2H, m,
NMR (300 MHz, DMSO-d ): δ 5–14 (1H, br s, OH),
6
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and NMR-Spectroscopic Investigations with
-Chloroacyl-1-phenylpyrazolin-5-ones
4
7
.68 (2H, m, Ph H-2,6), 7.47 (2H, m, Ph H-3,5), 7.28 (1H,
H O: C, 66.43; H, 5.08; N, 8.16. Found: C, 66.14; H,
2
m, Ph H-4), 3.64 (2H, m, ClCH ), 2.86 (2H, m, COCH ),
4.95; N, 8.05.
2
2
(
2E)-3-(2-Chlorophenyl)-1-(5-hydroxy-3-methyl-1-phenyl-
2
.42 (3H, s, Me), 1.73 (2H, m, ClCH CH ), 1.68 (2H, m,
2 2
1
3
1H-pyrazol-4-yl)prop-2-en-1-one (3g). This compound was
obtained in 86% yield as orange needles; mp 162–163°C
COCH CH CH ); C NMR (125 MHz, CDCl ): δ 196.8
2
2
2
3
2
(CO), 160.2 (pyrazole C-5), 147.3 (pyrazole C-3, J(C3,
1
(aqueous ethanol). H NMR (400 MHz, CDCl ): δ 11–15
Me) = 6.9 Hz), 137.1 (Ph C-1), 129.1 (Ph C-3,5), 126.6
3
3
3
(1H, very br s, OH), 8.30 (1H, d, J = 15.6 Hz, =CH-Ph),
7.92 (2H, m, NPh H-2,6), 7.70 (1H, m, CPh H-6), 7.47
(
Ph C-4), 120.6 (Ph C-2,6), 103.6 (pyrazole C-4, J(C4,
1
Me) = 2.6 Hz), 44.5 (ClCH2, J = 149.6 Hz), 38.1
(1H, m, CPh H-3), 7.44 (2H, m, NPh H-3,5), 7.36 (1H,
(
COCH ), 31.9 (ClCH CH ), 21.5 (COCH CH ), 15.8
2 2 2 2 2
13
1
m, CPh H-4), 7.35 (1H, m, CPh H-5), 7.25 (1H, m, NPh
(Me, J = 128.4 Hz); C NMR (75 MHz, DMSO-d ): δ
6
3
H-4), 7.17 (1H, d, J = 15.6 Hz, COCH=), 2.57 (3H, s,
1
94.6 (CO), 159.8 (pyrazole C-5), 150.0 (pyrazole C-3),
1
CH ); H NMR (400 MHz, DMSO-d ): δ 8.05 (1H, br d,
1
36.6 (Ph C-1), 129.0 (Ph C-3,5), 125.9 (Ph C-4), 120.5
3
6
3
3
J = 15.8 Hz, COCH=), 7.93 (1H, d, J = 15.8 Hz, =CH-
(
(
(
Ph C-2,6), 104.3 (pyrazole C-4), 45.2 (ClCH ), 38.7
2
Ph), 7.86 (1H, m, CPh H-6), 7.71 (2H, m, NPh H-2,6),
7.54 (1H, m, CPh H-3), 7.49 (2H, m, NPh H-3,5), 7.43
(2H, m, CPh H-4,5), 7.29 (1H, m, NPh H-4), 5–8
COCH ), 31.7 (ClCH CH ), 21.2 (COCH CH ), 14.2
2
2
2
2
2
15
Me); N NMR (50 MHz, CDCl ): δ À103.0 (N-2),
3
+
+
À191.2 (N-1); ms (m/z, %): 294 (M , 10), 292 (M ,31),
57 (21), 229 (28), 201 (100). Anal. Calcd. for
C H ClN O ∙ 0.1 H O: C, 61.16; H, 5.89; N, 9.51.
13
(1H, very br s, acidic H), 2.51 (3H, s, CH3); C NMR
2
(100 MHz, CDCl ): δ 177.8 (CO), 165.0 (pyrazole C-5),
3
15
17
2
2
2
1
46.9 (pyrazole C-3), 139.6 (=CH-Ph), 137.6 (NPh C-1),
Found: C, 60.86; H, 5.85; N, 9.50.
1
35.6 (CPh C-2), 132.7 (CPh C-1), 131.6 (CPh C-4),
2
-(2-Chlorophenyl)-1-(5-hydroxy-3-methyl-1-phenyl-1H-
pyrazol-4-yl)ethan-1-one (3e).
This compound was
130.5 (CPh C-3), 129.0 (NPh C-3,5), 128.0 (CPh C-6),
obtained in 88% yield as almost colorless crystals; mp
127.2 (CPh C-5), 125.9 (NPh C-4), 121.8 (COCH=),
1
13
1
40°C (aqueous ethanol).
H
NMR (300 MHz,
119.9 (NPh C-2,6), 105.0 (pyrazole C-4), 16.5 (Me);
NMR (100 MHz, DMSO-d ): δ 181.2 (CO), 161.2
6
C
DMSO-d ): δ 13.20 (1H, br s, OH), 7.68 (2H, m, NPh
6
H-2,6), 7.50 (2H, m, NPh H-3,5), 7.41 (1H, m, Ph H-3),
(pyrazole C-5), 150.8 (pyrazole C-3), 136.2 (NPh C-1),
135.2 (=CH-Ph), 134.0 (CPh C-2), 132.8 (CPh C-1),
131.5 (CPh C-4), 130.1 (CPh C-3), 129.0 (NPh C-3,5),
127.9 (CPh C-6), 127.8 (CPh C-5), 126.9 (COCH=),
125.9 (NPh C-4), 120.5 (NPh C-2,6), 104.9 (pyrazole C-
7
.32 (1H, m, Ph H-6), 7.30 (1H, m, NPh H-4), 7.27 (1H,
m, Ph H-5), 7.25 (1H, m, Ph H-4), 4.35 (2H, s, CH ),
2
1
3
2
1
1
1
1
.44 (3H, s, Me); C NMR (75 MHz, DMSO-d ): δ
90.8 (CO, J(CO,CH ) = 6.3 Hz), 159.8 (pyrazole C-5),
6
3
2
15
4
), 14.4 (Me), N NMR (40 MHz, CDCl ): δ À93.0
50.5 (pyrazole C-3), 136.0 (NPh C-1), 134.4 (Ph C-1),
33.8 (Ph C-2), 132.2 (Ph C-6), 129.0 (NPh C-3,5),
28.7 (Ph C-3), 128.1 (Ph C-4), 126.8 (Ph C-5), 126.0
3
(pyrazole N-2), À190.8 (pyrazole N-1); ms (m/z, %): 340
+ +
(M , 9), 338 (M , 28), 303 (100), 200 (74), 77 (88).
Anal. Calcd. for C H ClN O : C, 67.36; H, 4.46; N,
(
4
(
NPh C-4), 120.8 (NPh C-2,6), 104.1 (pyrazole C-4),
19 15
2 2
1
1
8.27. Found: C, 67.10; H, 4.35; N, 8.14.
4.8 (CH , J = 128.6 Hz), 13.8 (Me, J = 130.3 Hz); ms
2
+
+
m/z, %): 328 (M , 4), 326 (M , 11), 202 (12), 201 (100).
Anal. Calcd. for C H ClN O : C, 66.16; H, 4.63; N,
1
8
15
2 2
Acknowledgments. The authors thank Dr. L. Jirovetz and Ing. P.
Unteregger for recording the mass spectra. The authors are
grateful to Ms. Laura Castoldi for repeating one experiment.
8
.57. Found: C, 65.88; H, 4.69; N, 8.46.
3
-(2-Chlorophenyl)-1-(5-hydroxy-3-methyl-1-phenyl-1H-
pyrazol-4-yl)propan-1-one (3f).
This compound was
obtained in 74% yield as almost colorless crystals; mp
1
8
3–85°C (aqueous ethanol). H NMR (300 MHz,
REFERENCES AND NOTES
DMSO-d ): δ 13.20 (1H, br s, OH), 7.65 (2H, m, NPh
6
H-2,6), 7.47 (2H, m, NPh H-3,5), 7.40 (1H, m, Ph H-3),
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7
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4001.
13
C
2
2
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[
[
[
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(
1
(
pyrazole C-5), 150.3 (pyrazole C-3), 138.9 (Ph C-1),
36.2 (NPh C-1), 132.9 (Ph C-2), 130.5 (Ph C-6), 129.1
Ph C-3), 129.0 (NPh C-3,5), 127.7 (Ph C-4), 127.2 (Ph
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(
2
2
2
+
+
ms (m/z, %): 342 (M , 9), 340 (M , 30), 306 (26), 305
100), 201 (77). Anal. Calcd. for C H ClN O ∙ 0.15
[
(
1
9
17
2 2
Journal of Heterocyclic Chemistry
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G. A. Eller and W. Holzer
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet