Electrolytic partial fluorination of organic compounds. 79. Anodic fluorination of spiropyrazoline-5,3′-chroman-4-ones and thiochromanone analogues. A route to aroyl fluoride derivatives

Article abstract of DOI:10.1021/jo0507587

Anodic fluorination of spiropyrazole-5,3′-chroman-4-ones and their thiochromanone analogues in dimethoxyethane containing Et₄NF-4HF resulted in ring opening of spiroheterocycles, which led to the formation of (5-pyrazolyl)methyl o-carbomethoxyp

Full text of DOI:10.1021/jo0507587

Electrolytic Partial Fluorination of Organic Compounds. 79.
Anodic Fluorination of Spiropyrazoline-5,3′-chroman-4-ones and
Thiochromanone Analogues. A Route to Aroyl Fluoride
Derivatives
Kamal M. Dawood† and Toshio Fuchigami*,‡
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt, and Department of Electronic
Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Japan
fuchi@echem.titech.ac.jp
Received April 14, 2005
Anodic fluorination of spiropyrazole-5,3′-chroman-4-ones and their thiochromanone analogues in
dimethoxyethane containing Et4NF‚4HF resulted in ring opening of spiroheterocycles, which led
to the formation of (5-pyrazolyl)methyl o-carbomethoxyphenyl ethers and their thioether analogues
via benzoyl fluoride derivatives.
Fluorinated heterocycles are well known to be highly
biologically active candidates.1-3 Therefore, we developed
the selective anodic fluorination of various heterocyclic
systems;4-8 however, there has been no report dealing
with anodic fluorination of spiroheterocycles thus far.
Chromanone,9,10 thiochromanone,11 and pyrazole12,13 de-
rivatives are biologically active heterocycles and have
been utilized in diverse agricultural and pharmaceutical
applications. Recently, we carried out anodic fluorination
of chromanones 2a,b and thiochromanones 3a,b, and it
was found that the fluorination took place at R to the
ring oxygen and sulfur atoms, respectively.14-16 These
facts prompted us to investigate anodic fluorination of
spiroheterocycles such as 1,3,4-triarylspiropyrazole-5,3′-
chroman-4-ones 4a,b and their thio-analogues 5a,b,
which have two different heterocyclic rings to be fluori-
nated.
Preparation of the Spiroheterocycles 4a,b and
5a,b. 1,3,4-Triarylspiropyrazole-5,3′-chroman-4-one de-
rivatives 4a,b were prepared from the reaction of (E)-3-
benzylidenechroman-4-ones 2a,b with the hydrazonoyl
chloride 1 in dry benzene and triethylamine at room
temperature as reported in the literature.17 1,3,4-Tri-
arylspiropyrazole-5,3′-thiochroman-4-one derivatives 5a,b
were similarly prepared from (E)-3-benzylidenethiochro-
man-4-ones 2a,b with hydrazonoyl chloride 3 under
reflux conditions (Scheme 1).
* To whom correspondence should be addressed. Fax: +81-45-924-
5406.
† Cairo University.
‡ Tokyo Institute of Technology.
(1) Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy,
J. R., Welch, J. T., Eds.; ACS Symposium Series 639; American
Chemical Society: Washington, DC, 1996.
(2) Hiyama, T. Organofluorine Compounds: Chemistry and Ap-
plications; Springer: Berlin, 2000.
(3) Narizuka, S.; Fuchigami, T. Bioorg. Med. Chem. Lett. 1995, 5,
1293.
(4) Fuchigami, T. In Organic Electrochemistry, 4th ed.; Lund, H.,
Hammerich, O., Eds.; Marcel Dekker: New York, 2001; pp 1035-1050.
(5) Fuchigami, T. In Advances in Electron-Transfer Chemistry;
Mariano, P. S., Ed.; JAI Press: Greenwich, CT, 1999; Vol. 6.
(6) Fuchigami, T.; Higashiya, S.; Hou, Y.; Dawood, K. M. Rev.
Heteroat. Chem. 1999, 19, 67.
Oxidation Potentials of the Spiroheterocycles
4a,b and 5a,b. The oxidation peak potentials (Eopx) of
compounds 4a,b and 5a,b were measured by cyclic
voltammetry in an anhydrous acetonitrile solution con-
taining 0.1 M Bu4N‚BF4 using platinum electrodes and
(7) Dawood, K. M. Tetrahedron 2004, 60, 1435.
(8) Fuchigami, T.; Tajima, T. In Fluorine-Containing Synthons;
Soloshonok, V. A., Ed.; ACS Symposium Series 911; Oxford University
Press/American Chemical Society: Washington, DC, 2005; Chapter 15.
(9) Xu, Z. Q.; Bucheit, R. W.; Stup, T. L.; Flavin, M. T.; Khilevich,
A.; Rezzo, J. D.; Lin, L.; Zembower, D. E. Bioorg. Med. Chem. Lett.
1998, 8, 2179.
(10) Harlow, G. R.; Halpert, J. R. J. Biol. Chem. 1997, 272, 5396.
(11) Wang, H. K.; Bastow, K. F.; Cosentino, L. M.; Lee, K. H. J.
Med. Chem. 1996, 39, 1975.
(14) Dawood, K. M.; Fuchigami, T. Tetrahedron Lett. 2001, 42, 2513.
(15) Dawood, K. M.; Fuchigami, T. J. Org. Chem. 2001, 66, 7691.
(16) Dawood, K. M.; Ishii, H.; Fuchigami, T. J. Org. Chem. 2001,
66, 7030.
(17) Raghunathan, R.; Shanmugasundaram, M.; Bhanumathi, S.;
Malar, P. J. E. Heteroat. Chem. 1998, 9, 327.
(12) Vicentini, C. B.; Mares, D.; Tartari, A.; Manfrini, M.; Forlani,
G. J. Agric. Food Chem. 2004, 52, 1898.
(13) Wheate, N. J.; Broomhead, J. A.; Collins, J. G.; Day A. I. Aust.
J. Chem. 2001, 54, 141.
10.1021/jo0507587 CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/18/2005
J. Org. Chem. 2005, 70, 7537-7541
7537

Dawood and Fuchigami
TABLE 2. Anodic Fluorination of
Spiropyrazoline-5,3′-chroman-4-one Derivatives 4a,b
SCHEME 1
TABLE 1. Oxidation Peak Potentials Eopx of the Starting
Substratesa
substrate 4
yield %b
charge passeda
F/mole
run
Ar
cell/solvent
6
Eopx/V vs SSCE
1
2
3
4
5
C6H5
undivided/DME
divided/DME
undivided/MeCN
undivided/DME9
undivided/MeCN
10
10
6
87 (85)
88 (83)
60
92 (89)
58
ox
p1
ox
p2
C6H5
substrate
X
Ar
C6H5
4-ClC6H4
C6H5
4-ClC6H4
E
E
C6H5
4-ClC6H4
4-ClC6H4
4a
4b
5a
5b
O
O
S
1.11
1.12
1.06
1.09
2.17
2.25
1.83
1.87
9
6
a Constant current (6 mA cm-2) was applied; anode and cathode
were Pt sheets (2 × 2 cm). b Determined on the basis of 19F NMR,
and the isolated yields are in parentheses.
S
a Pt electrodes; 0.1 M Bu4NBF4/MeCN. Sweep rate 100 mV s-1
.
and 13C NMR), the structure 6b was further unequivo-
cally confirmed by carrying out its single-crystal X-ray
analysis.
Acetonitrile was found to be not so effective for the
anodic fluorination of these heterocyclic systems (runs 3
and 5, Table 2). The use of a divided cell did not affect
on the product yield (run 2, Table 2).
a saturated calomel electrode (SCE) as a reference
electrode. All the compounds 4a,b and 5a,b showed two
irreversible waves in their cyclic voltammograms as
shown in Table 1. The oxidation peak values (Eopx) of the
spirochromanones are higher than those of their thio-
analogues.
Anodic Fluorination of Spiropyrazoline-5,3′-chro-
man-4-ones 4a,b and Their Thio-Derivatives 5a,b.
Electrolytic fluorination of 1,3,4-triphenylspiropyrazoline-
5,3′-chroman-4-one (4a) was carried out with platinum
electrodes in a 0.3 M Et4NF‚4HF in dimethoxyethane
using a divided cell under a nitrogen atmosphere at room
temperature. A constant current was applied until the
starting substrate 4a was completely consumed. The
anodic fluorination was found to be straightforward and
afforded only one isolable product as examined by TLC.
It was expected that a fluorine atom would be introduced
to the position R to the oxygen atom of chromanone
moiety similarly to our reported results.14,15 However, the
19F NMR spectrum of the electrolysis product showed the
absence of any doublet signal, and only a singlet appeared
at δ -128.84 ppm, which implies that a proton at the
4-position of the pyrazole ring might be replaced by a
fluorine atom to give the 4-fluorospiropyrazole derivative
Next, anodic fluorination of the 1,3,4-triphenylspiro-
pyrazoline-5,3′-thiochroman-4-one (5a) was first under-
taken under a constant current (6 mA cm-2) using a
divided cell as shown in Table 3 (run 1).
The fluorination reaction resulted in the formation of
the benzoyl fluoride derivative 9a, similar to 6a, in a
moderate yield (46%) in addition to the difluorinated
product 10a in 7% yield. The benzoyl fluoride derivative
9a was obtained solely in a high yield (Table 3, run 2)
when compound 5a was anodically fluorinated under
constant applied potential of 1.06 V versus SCE, which
is the first oxidation potential of 5a. Constant potential
electrolysis of compound 5a at its second oxidation peak
potential (Eopx ) 1.83 V versus SCE) resulted in the
reversed product selectivity and led to the formation of
the difluorinated derivative 10a as the major product in
addition to a small amount (8%) of the benzoyl fluoride
9a (Table 3, run 3).
1
7a (Table 2). The H NMR spectrum revealed also the
presence of the methylene protons R to the oxygen atom
and the absence of the methine proton of the pyrazole
moiety, which rules out the possibility of the formation
of structure 8a. The 13C NMR spectrum showed, however,
only one sp3 carbon at δ 60.31. All these spectral data
strongly support the structure 6a and rule out the other
structures 7a and 8a. In addition, anodic fluorination of
the spiropyrazoline-5,3′-chroman-4-one derivative 4b was
similarly attempted using Et4NF‚4HF in dimethoxy-
ethane to give the benzoyl fluoride derivative 6b in
excellent yield. In addition to spectral data (MS, 1H, 19F,
Furthermore, the anodic behavior of the 4-(4-chlo-
rophenyl)-1,3-diphenylspiropyrazoline-5,3′-thiochroman-
4-one (5b) was similarly studied, and the results are
shown in Table 3 (runs 4-6). Galvanostatic electrolysis
of 5b afforded mono- and difluorinated derivatives 9b and
10b, respectively, in equivalent yields (about 30%, each)
(run 4). On the other hand, when the electrolysis was
carried out under controlled potential condition at 1.10
V versus SSCE (the first oxidation potential of 5b), the
benzoyl fluoride derivative 9b was obtained exclusively
in 97% yield (Table 3, run 5). Constant potential elec-
7538 J. Org. Chem., Vol. 70, No. 19, 2005

Electrolytic Partial Fluorination of Organic Compounds
TABLE 3. Anodic Fluorination of
SCHEME 2
Spiropyrazoline-5,3′-thiochroman-4-one Derivative 5a,b
SCHEME 3
substrate 5
yield %b
9
10c 11d
charge passed
F/mole
applied
run
Ar
electrolysisa
1
2
3
4
5
6
C6H5
10
8
6 mA cm-2 46
7
-
-
C6H5
+1.06 Va
+1.83 Va
89 (80)
8
-
C6H5
8
56 (71)
4-ClC6H4
4-ClC6H4
4-ClC6H4
10
7
8
6 mA cm-2 32 (25) 30 (46)
+1.1 Va
97 (95)
15 (9) 65 (88)
-
-
+1.87 Va
a Versus SSCE, anode and cathode were Pt sheets (2 × 2 cm)
using a divided cell. b Determined on the basis of 19F NMR, and
the values in parentheses indicate the isolated yields. c Unstable
products and readily converted into 5-formylpyrazoles 11a,b when
left at room temperature or during the working up. Structures of
10a,b were established by 19F NMR. d Isolated yields after column
chromatography of the crude reaction mixture.
trolysis of compound 5b at its second oxidation peak
potential (Eopx ) 1.87 V versus SCE) furnished the
difluorinated derivative 10b as the major product (65%)
along with a minor yield of the benzoyl fluoride derivative
9b (15%) (Table 3, run 6).
The fluorinated products 10a,b are unstable under the
purification conditions using silica gel chromatography;
therefore their structures were identified on the basis of
their 19F NMR spectra [10a: δ -60.57 (d, 1F, J ) 53.64
Hz), -136.45 (s, 1F). 10b: δ -61.24 (d, 1F, J ) 51.79
Hz), -135.10 (s, 1F)] of the crude reaction products. It is
noted that compounds 10a,b were completely converted
into the 5-formylpyrazole derivatives 11a,b when they
were either passed through silica gel column chromatog-
raphy or left at room temperature for 2 days in open air,
and their isolated yields are shown in Table 3.
cation A undergoes cleavage of the carbon-carbon bond
between the carbonyl-carbon and the spirocarbon to
form a benzoyl cation at one terminal and a pyrazolinyl
radical at the other terminal of the intermediate B. The
benzoyl cation of B reacts with a fluoride ion, and the
pyrazolinyl radical is subsequently oxidized to give the
corresponding cation C, which undergoes deprotonation
to give pyrazole derivative 9a. In the electrolysis at the
second oxidation peak potential, further anodic oxidation
of compound 9a took place to form the difluorinated
derivative 10a via the cationic intermediate D. The
fluorine atom R to the sulfur in compound 10a can be
easily nucleophilically attacked by a hydroxide ion from
the moisture to form the thioacetal intermediate E, which
is easily converted into the corresponding 5-formylpyra-
zole derivative 11a (Scheme 3).
Chemical evidence for the presence of the acyl fluoride
moiety in the electrolytic products 6a,b and 9a,b was
further confirmed by their treatment with methanol to
give the corresponding methyl esters 12a,b and 13a,b,
respectively (Table 4).
Previously, Yoneda at al. reported anodic fluorination
of alkyl aldehydes to provide acyl fluorides selectively.18
However, in the case of aromatic aldehydes, the aromatic
ring fluorination always took place as a side reaction. On
the contrary, in our case, the benzene ring was not
fluorinated at all.
In addition, the oxidation peak potential of the benzoyl
fluoride derivative 9b was measured by cyclic voltam-
metry under the same conditions as described in Table
1. Compound 9b showed two irreversible oxidation peaks
at 1.80 and 2.10 V versus SSCE. Controlled potential
electrolysis of 9b at 1.80 V versus SSCE afforded the
difluorinated product 10b in 61% yield estimated by 19
F
NMR of the crude product. Purification through silica gel
column chromatography resulted in the formation of pure
5-formylpyrazole derivative 11b in 86% yield as shown
in Scheme 2.
A plausible mechanism for the anodic formation of the
benzoyl fluoride derivative 9a and the aldehyde deriva-
tive 11a from the spiroheterocycle 5a is depicted in
Scheme 3. Since the spiroheterocycles have oxidation
potentials (ca. 1 V versus SSCE) much lower than those
of thiochromanones and chromanones (ca. ∼1.7-2 V
versus SSCE),15,16 the initial electron transfer seems to
take place at the pyrazole ring. The resulting radical
(18) Yoneda, N.; Chen, S. Q.; Hatakeyama, T.; Hara, S.; Fukuhara,
T. Chem. Lett. 1994, 849.
J. Org. Chem, Vol. 70, No. 19, 2005 7539

Dawood and Fuchigami
TABLE 4. Esterification of Acyl Fluorides 6a,b and 9a,b
erocycle 4a,b or 5a,b (1 mmol). The electrolysis was performed
in a divided or an undivided cell under a nitrogen atmosphere
at room temperature. A constant current (6 mA cm-2) or
controlled potential electrolyte was applied until the starting
substrate was completely consumed (monitored by TLC and
GC-MS). After the electrolysis, the solution was passed
through a short column of silica gel using ethyl acetate as an
eluent. The eluents were evaporated under reduced pressure,
and then the yield of the fluorinated product was calculated
by means of 19F NMR by using a known amount of monofluo-
robenzene as an internal standard. The yields were calculated
on the basis of the integral ratios between the monofluoroben-
zene and the fluorinated products. The products were purified
by column chromatography using ethyl acetate/hexane mixture
(1:5) as an eluent.
run
X
substrate
product
yield %a
1
2
3
4
O
O
S
6a
6b
9a
9b
12a
12b
13a
13b
94
98
83
85
S
a Isolated yields.
5-(2-Fluorocarbonyl)phenoxymethyl-1,3,4-triphenyl-
1
pyrazole (6a): mp 158-159 °C; H NMR (CDCl3) δ 4.94 (s,
2H), 6.80 (d, 1H, J ) 8.41 Hz), 7.06 (dd, 1H, J ) 7.75, 7.58
Hz), 7.25-7.57 (m, 14H), 7.79 (d, 2H, J ) 7.75 Hz), 7.95 (d,
1H, J ) 7.91 Hz); 19F NMR δ -128.84 (s); 13C NMR (DEPT) δ
60.31 (CH2), 113.47, 121.12, 124.84, 127.31, 127.67, 128.10,
128.51, 129.17, 130.15, 133.82, 133.88, 136.32 (CH), 114.08,
123.75, 132.35, 132.59, 134.97, 139.20, 149.60, 154.74 (d, J )
343.18 Hz), 159.08 (C). MS (m/z): 448 (M+), 343, 309, 231, 204,
193, 168, 149, 77, 58. Anal. Calcd for C29H21FN2O2: C, 77.66;
H, 4.77; N, 6.25. Found: C, 77.31; H, 4.82; N, 6.24.
4-(4-Chlorophenyl)-5-(2-fluorocarbonyl)phenoxymethyl-
1,3-diphenylpyrazole (6b): mp 163 °C; 1H NMR (CDCl3): δ
4.90 (s, 2H), 6.84 (d, 1H, J ) 8.24 Hz), 7.09 (t, 1H, J ) 7.58
Hz), 7.29-7.54 (m, 13H), 7.76 (d, 2H, J ) 8.08 Hz), 7.98 (d,
1H, J ) 7.91 Hz); 19F NMR δ -128.76 (s); 13C NMR (DEPT) δ
60.26 (CH2), 113.35, 121.31, 124.82, 127.86, 128.12, 128.25,
128.78, 129.24, 131.41, 133.92, 136.40 (CH), 114.14, 122.61,
130.87, 132.33, 133.39, 134.99, 139.04, 149.63, 154.66 (d, J )
343.18 Hz), 159.01 (C). MS (m/z): 484 (M+ + 2), 482 (M+), 358,
343, 308, 265, 204, 180, 123, 105, 77, 58. Anal. Calcd. for
C29H20ClFN2O2: C, 72.12; H, 4.17; N, 5.80. Found: C, 71.99;
H, 4.31; N, 5.80.
5-(2-Fluorocarbonyl)phenylthiomethyl-1,3,4-triphen-
ylpyrazole (9a): mp 126-127 °C; 1H NMR (CDCl3) δ 4.16
(s, 2H), 7.12 (d, 1H, J ) 8.08 Hz), 7.18-7.48 (m, 15H), 7.72 (d,
2H, J ) 7.42 Hz), 7.96 (d, 1H, J ) 7.75 Hz); 19F NMR δ -136.45
(s); 13C NMR (DEPT) δ 27.17 (CH2), 124.71, 125.45, 126.61,
127.23, 127.58, 127.98, 128.07, 128.38, 128.54, 129.21, 130.14,
133.12, 134.58 (CH), 132.60, 132.65, 134.85, 139.27, 143.87,
143.99, 149.86, 155.30 (d, J ) 343.74 Hz), (C). MS (m/z): 464
(M+), 327, 309, 281, 221, 207, 147, 95, 69. Anal. Calcd for
C29H21FN2OS: C, 74.98; H, 4.56; N, 6.03; S, 6.90. Found: C,
74.81; H, 4.42; N, 6.21; S, 6.83.
4-(4-Chlorophenyl)-5-(2-fluorocarbonyl)phenylthio-
methyl-1,3-diphenylpyrazole (9b): mp 140-141 °C; 1H
NMR (CDCl3) δ 4.13 (s, 2H), 7.14 (d, 1H, J ) 8.08 Hz), 7.20-
7.31 (m, 8H), 7.40-7.49 (m, 6H), 7.71 (dd, 2H, J ) 8.08, 1.48
Hz), 7.97 (dd, 1H, J ) 7.91, 1.48 Hz); 19F NMR δ -136.27 (s);
13C NMR δ 27.13, 120.66, 121.20, 122.07, 124.90, 125.41,
126.59, 126.65, 127.76, 127.97, 128.16, 128.18, 128.49, 128.80,
129.24, 131.16, 131.39, 132.32, 133.16, 133.24, 134.64, 134.90,
139.08, 143.54, 143.66, 149.88, 155.31 (d, J ) 343.74 Hz). MS
(m/z): 500 (M+ + 2), 498 (M+), 343, 308, 204, 180, 77, 58. Anal.
Calcd for C29H20ClFN2OS: C, 69.80; H, 4.04; N, 5.61; S, 6.43.
Found: C, 69.44; H, 4.06; N, 5.73; S, 6.43.
In summary, we have shown the first example of the
electrochemical synthesis of aroyl fluorides through
anodic fluorination accompanied with ring opening of
spiroheterocycles.
Experimental Section
Hydrazonoyl chloride 1,19 3-benzylidene derivatives of chro-
manones 2a,b, and thiochromanones 3a,b20 were prepared
according to the procedures described in the literature.
4-Aryl-1,3-diphenylspiropyrazoline-5,3′-thiochroman
4-ones 5a,b. To a mixture of the hydrazonoyl chloride 3 (2
mmol) and the appropriate (E)-3-arylidenethiochroman-4-one
2a or 2b (2 mmol) in dry benzene (20 mL), triethylamine (0.2
mL) was added, and the reaction mixture was refluxed for 30-
36 h. After the reaction was complete, it was left to cool to
room temperature. The solvent was removed under reduced
pressure, and the residue was triturated with methanol to give
yellow precipitates that were collected by filtration, washed
with methanol, and dried. The products were further purified
by recrystallization from dioxane/water to afford the corre-
sponding spiroheterocycles 5a,b.
1,3,4-Triphenylspiropyrazoline-5,3′-thiochroman-4-
one (5a): Yield (79%); mp 160-161 °C; IR (KBr) ν 1681 (Cd
O), 1583 (CdN) cm-1; 1H NMR (CDCl3) δ 2.88 (d, 1H, J ) 13.52
Hz), 4.31 (d, 1H, J ) 13.52 Hz), 4.83 (s, 1H), 6.96 (m, 1H),
7.17-7.57 (m, 17H), 8.14 (d, 1H, J ) 7.83 Hz); 13C NMR δ
30.51, 60.75, 75.73, 118.93, 121.72, 125.28, 126.09, 126.87,
128.12, 128.20, 128.27, 128.40, 128.60, 128.64, 131.15, 131.38,
133.88, 134.66, 140.85, 143.14, 149.10, 189.47. MS m/z, 447
(M+ + 1), 446 (M+), 341, 310, 233, 206, 178, 154, 107, 69. For
C29H22N2OS calcd: C, 78.00; H, 4.97; N, 6.27; S, 7.18. Found:
C, 78.13; H, 5.03; N, 6.16; S, 7.11%.
4-(4-Chlorophenyl)-1,3-diphenylspiropyrazoline-5,3′-
thiochroman-4-one (5b): Yield (83%); mp 163-164 °C; IR
(KBr) ν 1687 (CdO), 1594 (CdN) cm-1 1H NMR (CDCl3) δ
;
2.83 (d, 1H, J ) 13.68 Hz), 4.31 (d, 1H, J ) 13.68 Hz), 4.80 (s,
1H), 6.97 (m, 1H), 7.17-7.28 (m, 12H), 7.39-7.54 (m, 4H), 8.13
(d, 1H, J ) 7.75 Hz); 13C NMR δ 30.54, 59.91, 75.79, 119.18,
122.02, 125.40, 126.03, 126.91, 128.22, 128.48, 128.63, 128.69,
131.08, 131.21, 133.21, 133.98, 134.14, 140.59, 143.04, 148.78,
189.09. MS m/z, 483 (M+ + 2), 482 (M+ + 1), 481 (M+), 375,
344, 281, 207, 178, 142, 77. For C29H21ClN2OS calcd: C, 72.41;
H, 4.40; N, 5.82; S, 6.67. Found: C, 72.60; H, 4.58; N, 5.89; S,
6.71%.
5-Formyl-1,3,4-triphenylpyrazole (11a): mp 122-123 °C;
1H NMR (CDCl3) δ 7.17-7.22 (m, 3H), 7.32-7.35 (m, 5H),
7.39-7.42 (m, 5H), 7.49-7.51 (m, 2H), 9.66 (s, 1H); 13C NMR
(DEPT) δ 125.67, 128.02, 128.11, 128.24, 128.49, 128.79,
130.58, 180.09 (CH), 128.91, 130.18, 131.47, 136.45, 139.36,
150.04 (C). MS (m/z): 324 (M+), 220, 188, 155, 124, 84. Anal.
Calcd for C22H16N2O: C, 81.46; H, 4.97; N, 8.64. Found: C,
81.25; H, 4.88; N, 8.56.
The 4-aryl-1,3-diphenylspiropyrazoline-5,3′-chroman-4-ones
4a,b were prepared at room temperature using the similar
procedure that was used in the synthesis of compounds 5a,b,
and the spectral data of the products 4a,b were in complete
accordance with those reported in the literature.17
Anodic Fluorination of 4-Aryl-1,3-diphenylspiropyra-
zoline-5,3′-chroman (thiochroman)-4-ones 4a,b and 5a,b.
Electrolysis was conducted with platinum electrodes (2 × 2
cm2) in 0.3 M solution of a fluoride salt in dimethoxyethane
or acetonitrile (20 mL) containing the appropriate spirohet-
(19) Wolkoff, P. Can. J. Chem. 1975, 53, 1333.
(20) Levai, A.; Schag, J. B. Pharmazie 1979, 34, 749.
7540 J. Org. Chem., Vol. 70, No. 19, 2005

Electrolytic Partial Fluorination of Organic Compounds
4-(4-Chlorophenyl)-1,3-diphenyl-5-formylpyrazole
(11b): mp 130-131 °C; 1H NMR (CDCl3) δ 7.31-7.35 (m, 5H),
7.38-7.41 (m, 2H), 7.46-7.57 (m, 7H), 9.76 (s, 1H); 13C NMR
(DEPT) δ 125.72, 128.11, 128.31, 128.37, 128.39, 128.76,
128.98, 131.90, 179.89 (CH), 126.75, 128.82, 131.27, 134.39,
136.52, 139.09, 150.23 (C). MS (m/z): 360 (M+ + 2), 359 (M+
+ 1), 358 (M+), 329, 227, 190, 165, 123, 77. Anal. Calcd for
C22H15ClN2O: C, 73.64; H, 4.21; N, 7.81. Found: C, 73.49; H,
3.97; N, 7.87.
Esterification of the Acyl Fluorides 6a,b and 9a,b. A
mixture of the appropriate acyl fluoride derivatives 6a,b or
9a,b (0.3 mmol) in methanol (3 mL) was heated at 60 °C for 1
h and then left to cool. The solvent was evaporated under
vacuum, and the residue was further purified by being passed
through silica gel column chromatography using ethyl acetate/
hexane (1:5) as an eleunt.
5-(2-Methoxycarbonyl)phenoxymethyl-1,3,4-triphen-
ylpyrazole (12a): mp 116-117 °C (EA/hexane); 1H NMR
(CDCl3) δ 3.78 (s, 3H), 4.78 (s, 2H), 6.67 (d, 1H, J ) 8.24 Hz),
6.91 (dd, 1H, J ) 7.42, 7.26 Hz), 7.19-7.35 (m, 12H), 7.44-
7.48 (m, 2H), 7.70-7.79 (m, 3H); 13C NMR (DEPT) δ 52.16
(CH3), 60.23 (CH2), 113.42, 120.94, 124.47, 127.12, 127.60,
127.81, 128.07, 128.41, 129.11, 130.04, 131.57, 133.07 (CH),
121.14, 123.62, 132.34, 132.68, 135.43, 139.28, 149.51, 156.58,
166.60 (C). MS (m/z): 461 (M+ + 1), 460 (M+), 309, 154, 136,
77, 69. Anal. Calcd for C30H24N2O3: C, 78.24; H, 5.25; N, 6.08.
Found: C, 78.08; H, 5.45; N, 5.99.
4-(4-Chlorophenyl)-5-(2-methoxycarbonyl)phenoxy-
methyl-1,3-diphenylpyrazole (12b): mp 120-121 °C; 1H
NMR (CDCl3) δ 3.88 (s, 3H), 4.86 (s, 2H), 6.79 (d, 1H, J ) 8.24
Hz), 7.03 (dd, 1H, J ) 7.41, 7.26 Hz), 7.25-7.55 (m, 14H), 7.83
(d, 2H, J ) 7.42 Hz); 13C NMR (DEPT) δ 52.19 (CH3), 60.21
(CH2), 113.37, 121.12, 124.46, 124.76, 127.79, 127.96, 128.15,
128.70, 129.17, 131.34, 131.63, 133.16 (CH), 122.46, 128.08,
130.86, 132.41, 133.34, 135.46, 139.11, 149.54, 156.51, 166.44
(C). MS (m/z): 496 (M+ + 2), 495 (M+ + 1), 494 (M+), 391,
343, 307, 289, 197, 154, 136, 69. Anal. Calcd. for C30H23-
ClN2O3: C, 72.80; H, 4.68; N, 5.66. Found: C, 72.64; H, 4.59;
N, 5.44.
1H, J ) 7.58, 7.42 Hz), 7.16-7.40 (m, 14H), 7.67 (d, 2H, J )
7.42 Hz), 7.82 (d, 1H, J ) 7.58 Hz); 13C NMR (DEPT) δ 52.18
(CH3), 27.62 (CH2), 124.55, 125.31, 126.68, 127.04, 127.50,
127.99, 128.02, 128.14, 128.41, 129.09, 130.11, 130.96, 132.23
(CH), 121.64, 128.10, 132.70, 135.63, 139.30, 140.03, 149.75,
166.54 (C). MS (m/z): 477 (M+ + 1), 476 (M+), 325, 309, 259,
231, 197, 154, 135. Anal. Calcd for C30H24N2O2S: C, 75.60; H,
5.08; N, 5.88; S, 6.73. Found: C, 75.41; H, 5.15; N, 5.69; S,
6.71.
4-(4-Chlorophenyl)-5-(2-methoxycarbonyl)phenylthi-
1
omethyl-1,3-diphenylpyrazole (13b): mp 117-118 °C; H
NMR (CDCl3) δ 3.82 (s, 3H), 4.01 (s, 2H), 7.02 (d, 1H, J ) 7.92
Hz), 7.10 (dd, 1H, J ) 7.75, 7.42 Hz), 7.19-7.39 (m, 13H), 7.67
(d, 2H, J ) 7.58 Hz), 7.85 (d, 1H, J ) 7.75 Hz); 13C NMR
(DEPT) δ 52.24 (CH3), 27.57 (CH2), 124.84, 125.41, 126.74,
127.99, 128.11, 128.26, 128.39, 128.78, 129.27, 131.16, 131.49,
132.31 (CH), 120.37, 127.66, 131.24, 132.45, 132.99, 135.65,
139.16, 139.79, 149.80, 166.50 (C). MS (m/z): 512 (M+ + 2),
511 (M+ + 1), 510 (M+), 308, 229, 194, 135, 77. Anal. Calcd
for C30H23ClN2O2S: C, 70.51; H, 4.54; N, 5.48; S, 6.27. Found:
C, 70.52; H, 4.49; N, 5.42; S, 6.31.
X-ray Crystallography of Compound 6b. X-ray diffrac-
tion measurements of compound 6b were made on a Rigaku
RAXIS IV imaging plate area detector with graphite-mono-
chromated Mo KR radiation (λ ) 0.71069 Å) at -60 °C. Crystal
data for 6b: C29H20O2ClF, fw ) 482.94, monoclinic, space
group P21/n, a ) 16.1589(7) Å, b ) 8.0433(2) Å, c ) 18.0403-
(7) Å, â ) 93.1640(10)°, V ) 2341.1(2) Å3, Z ) 4, dcalcd ) 1.37
g‚cm-3, µ ) 2.01 cm-1, R1 ) 0.051 for the 2879 unique data
with F > 4σ(F) (wR2 ) 0.149 for all 4967 data) and 316
parameters.
Acknowledgment. We thank Prof. M. Akita of the
Tokyo Institute of Technology for X-ray analysis. K.M.D.
is greatly indebted to the JSPS for awarding him a
postdoctoral fellowship (1999-2001).
Supporting Information Available: General part, gen-
eral experimental method, X-ray data, and cyclic voltammo-
grams of 4a, 4b, 5a, and 5b. This material is available free of
charge via the Internet at http://pubs.acs.org.
5-(2-Methoxycarbonyl)phenylthiomethyl-1,3,4-tri-
phenylpyrazole (13a): mp 110-111 °C; 1H NMR (CDCl3) δ
3.80 (s, 3H), 4.03 (s, 2H), 6.99 (d, 1H, J ) 8.08 Hz), 7.06 (dd,
JO0507587
J. Org. Chem, Vol. 70, No. 19, 2005 7541