Synthesis of polyfunctional β-Ketosulfides and their reactions with m-chloroperbenzoic acid and chlorine dioxide

Article abstract of DOI:10.1134/S107042801302005X

The reaction of bromoacetophenone with various thiols furnished β-ketosulfides: 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-1-phenylethanone, 2-(1H-imidazol-2-ylsulfanyl)-1-phenylethanone, 2-(2-hydroxyethylsulfanyl)-1- phenylethanone. β-Ketosulfoxides were obta

Full text of DOI:10.1134/S107042801302005X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 2, pp. 204−207. © Pleiades Publishing, Ltd., 2013.
Original English Text © Yu.V. Krymskaya, I.V. Loginova, S.A. Rubtsova, A.V. Kuchin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 2,
pp. 215−218.
Synthesis of Polyfunctional β-Ketosulfides
and Their Reactions with m-Chloroperbenzoic Acid
and Chlorine Dioxide
Yu. V. Krymskaya, I. V. Loginova, S. A. Rubtsova, and A. V. Kuchin
Institute of Chemistry, Komi Scientific Center, Ural Branch of Russian Academy of Sciences,
Syktyvkar, 167982 Russia
e-mail: rubtsova-sa@chemi.komisc.ru
Received May 14, 2012
Abstract—Thereactionofbromoacetophenonewithvariousthiolsfurnishedβ-ketosulfides:2-(1-methyl-1H-imidazol-
2-ylsulfanyl)-1-phenylethanone, 2-(1H-imidazol-2-ylsulfanyl)-1-phenylethanone, 2-(2-hydroxyethylsulfanyl)-1-
phenylethanone. β-Ketosulfoxides were obtained by the oxidation of β-ketosulfides with m-chloroperbenzoic acid
and chlorine dioxide.
DOI: 10.1134/S107042801302005X
with chlorine dioxide of γ-ketosulfides [4] and
polyfunctional sulfides containing triazole, tetrazole, or
benzimidazole groups [5].
Polyfunctional ketosulfoxides alongside two active
sites, sulfinyl and carbonyl groups that underlie their
reactivity, may have in the molecule the other functional
groups providing them with specific properties.
In this article results are presented of the oxidation
of polyfunctional β-ketosulfides containing imidazole
or hydroxy groups.
Imidazol-containing sulfides, sulfoxides, and
sulfones possess the antimicrobial action [1].
Hydroxyalkyl sulfides are interesting for the production
of lubricants, anion exchangers, dyes, organic solvents,
polymers, polymer stabilizers, plasticizers, supplying
the polymers with stability against heat and freezing,
against light [2]. Hydroxysulfoxides are characterized
by many typical reactions of the sulfinyl and hydroxy
groups. They can be converted into hydroxysulfones,
β-oxo- and acetoxysulfoxides [3].
Initial β-ketosulfides Ia–Ic were obtained in 42–69%
yields by the reaction of bromoacetophenone with ap-
propriate thiols in alkaline alcoholic medium (Scheme 1).
The structure of compounds Ia–Ic was established
from TR and NMR spectra (see EXPERIMENTAL).
At the oxidation of sulfides Ia–Ic with m-chloroper-
benzoic acid at 20°C, molar ratio sulfide–oxidant 1 :
1, and the complete conversion of the initial sulfides
We formerly reported on a chemoselective oxidation
Scheme 1.
O
O
S
O
O
6
A
3
R
S
R
Br
7
5
4
KOH, EtOH
[O]
1
2
8
A
HS
R
+
IIа_IIc
Iа_Ic
3
N
3
4
4
N
2
OH
2
1
2
(c).
(b),
5
(a),
5
В
В
1N
R =
1N
H
6
204

SYNTHESIS OF POLYFUNCTIONAL β-KETOSULFIDES
205
Scheme 2.
O
O
N
N
S
S
Cl
ClO2
N
R
N
R
IIa +
Ia
III
R = Me, H.
β-ketosulfoxides IIa–IIc free of sulfones formed in
47–53% yields. Further increase in the proportion of the
oxidant resulted in the tarring of the reaction mixture.
At the oxidation of β-ketosulfides Ib, Ic with ClO2
under the same conditions the yield of β-ketosulfoxides
IIb, IIc reached 98 and 54% respectively.
1H NMR spectra of compounds IIa, IIb contained
the proton signals from the imidazole and aromatic
fragments. The signals of the diastereotopic protons of
the methylene groups in the position 8 are observed as
two doublets in the region δ 5.25–5.30 and 5.15–5.20 ppm
with the coupling constant of 15.5 Hz characteristic of
the geminal protons.
Thus the oxidation of the N-substituted β-ketosulfide
with ClO2 led to the formation of the chlorination
products. m-Chloroperbenzoic acid is more preferable
oxidant for these compounds. ClO2 is a promising oxidant
for the preparation of N-unsubstituted β-ketosulfoxides.
EXPERIMENTAL
In the 1H NMR spectrum of compound IIc the signals
of the protons of the aromatic ring remained. The presence
of the chiral sulfur aton in the sulfoxide group affects
the methylene protons present in the α-position with
respect to the asymmetric center. These protons become
nonequivalent and appear in the spectrum as two doublets
in the region of 4.66 and 4.70 ppm, analogous to the
spectra of compounds IIa, IIb.
IR spectra were recorded on a spectrophotometer
1
Prestige-21 from pellets with KBr. H and 13C NMR
spectra were registered on a spectrometer BrukerAvance
II-300 (300 and 75 MHz respectively) from solutions
in deuterated DMSO. Mass spectra were measured on
an instrument Thermo DSQ (Direct Probe System), EI
ionization, ionizing electrons energy 70 eV. Elemental
analysis was carried out on an automatic analyzer
EA1110 CHNS-O. Melting points were measured on an
instrument Sanyo gallenkamp equipped with a digital
thermometer. The reaction products were isolated by
column chromatography on silica gelAlfaAesar 70/230μ.
TLC was performed on Sorbfil plates, eluent tert-butyl
methyl ether, developer 5% solution of potassium
permanganate. The ClO2 solution in organic solvent
was prepared by bubbling ClO2 from the water solution
(c 7 g L–1) through the organic solvent cooled to 0°C.
At the oxidation of N-substituted β-ketosulfide Ia
with chlorine dioxide the main reaction product was
2-(5-chloro-1-methyl-1H-imidazol-2-ylsulfanyl)-1-
phenylethanone (III) (yield 47%), the yield of sulfoxide
(IIa) ≤8% (Scheme 2).
The absence in the 1H NMR spectrum of compound
III of the proton signal in the position 5 of the imidazole
fragment indicates its replacement. The proton signals
1
of the methylene group in the H NMR spectrum are
not shifted downfield showing that the sulfoxide group
is absent.
β-Ketosulfides. General procedure. To a solution
of 5.6 g (0.1 mol) of KOH in 30 ml of ethanol heated to
50°C was added at stirring 1.14 g (0.1 mol) of 1-methyl-
1H-imidazole-2-thiol and 19.9 g (0.1 mol) of bromo-
acetophenone. The reaction mixture was stirred for 3 h.
The solution was cooled and water was added till the
precipitate dissolved. The reaction product was extracted
with tert-butyl methyl ether, the extract was washed with
5% NaOH solution (50 × 2 ml), and dried with Na2SO4.
The solvent was evaporated, the reaction products were
isolated by chromatography.
The assignment of the signals in the 1H and 13C NMR
spectra was done with the use of 2D spectra HMCC and
HSQC. In the heteronuclear HSQC spectrum a cross-peak
was observed due to the coupling of the proton with the
carbon atom in the position 4, and no cross-peak existed
from the coupling of a proton with a carbon atom in the
position 5 indicating that no proton substitution occurred
at the atom C5. In the HMCC spectrum a cross-peak was
observed from the coupling of the methyl protons of the
NCH3 group and the quaternary atom C5.
2-(1-Methyl-1H-imidazol-2-ylsulfanyl)-1-phenyl-
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KRYMSKAYA et al.
206
ethanone (Ia). Yield 51%. Light-yellow crystals, mp
65–66°C. IR spectrum, ν, cm–1: 1678 (C=O), 686 (C–S).
1H NMR spectrum, δ, ppm: 3.57 s (3H, C6CH3), 4.65 s
(2H, C8H2), 6.90 s (1H, C4CH), 7.23 s (1H, C5CH), 7.54 t
(2H, C3AH, C5AH, J 7.3 Hz), 7.68 t (1H, C4AH, J 7.3 Hz),
7.97 d (2H, C2AH, C6AH, J 7.1 Hz). 13C NMR spectrum,
δ, ppm: 33.35 (C6C), 41.48 (C8), 123.89 (C5C), 128.88
(C3A, C5A), 129.09 (C4C), 129.22 (C2A, C6A), 134.01
(C4A), 135.81 (C1A), 139.59 (C2C), 194.50 (C7). Found, %:
C 62.12; H 5.21; N 11.97; S 13.86. C12H12N2OS. Calcu-
lated, %: C 62.07; H 5.17; N 12.07; S 13.79.
with brine and water, dried with Na2SO4. The solvent
was evaporated, the reaction products were isolated by
chromatography.
2-(1-Methyl-1H-imidazol-2-sulfinyl)-1-phenyle-
thanone (IIa). Yield 0.124 g (50%) (a), 0.021 g (8%)
(b). White crystals, mp 102°C. IR spectrum, ν, cm–1:
1
1044 (S=O). H NMR spectrum, δ, ppm: 3.93 s (3H,
C6CH3), 5.25 d (1H, C8H2, J 15.5 Hz), 5.30 d (1H, C8H2,
J 15.5 Hz), 7.13 s (1H, C4CH), 7.45 s (1H, C5CH), 7.58 t
(2H, C3AH , C5AH, J 7.5 Hz), 7.73 t (1H, C4AH, J 7.4 Hz),
8.02 d (2H, C2AH, C6AH, J 7.5 Hz). 13C NMR spectrum,
δ, ppm: 33.66 (C6C), 61.46 (C8), 126.09 (C5C), 129.02
(C4C, C3A, C5A), 129.38 (C2A, C6A), 134.66 (C4A), 135.91
(C1A), 146.08 (C2C), 193.45 (C7). Found, %: C 57.98;
H 4.87; N 11.35; S 12.96. C12H12N2O2S. Calculated, %:
C 58.06; H 4.84; N 11.29; S 12.90.
2-(1H-Imidazol-2-ylsulfanyl)-1-phenylethanone
(Ib). Yield 42–50%. Light-yellow crystals, mp 158–
159°C. IR spectrum, ν, cm–1: 1686 (C=O), 694 (C–S).
1H NMR spectrum, δ, ppm: 4.70 s (2H, C8H2), 7.04 s (2H,
C4CH, C5CH), 7.55 t (2H, C3AH, C5AH, J 7.5 Hz), 7.68 t
(1H, C4AH, J 7.5 Hz), 8.01 d (2H, C2AH, 6AH, J 9 Hz),
12.30 s (1H, N1CH). 13C NMR spectrum, δ, ppm: 40.88
(C8), 126.58 (C4C, C5C), 128.90 (C3A, C5A), 129.22 (C2A,
C6A), 133.65 (C4A), 135.82 (C1A), 138.37 (C2C), 194.55
(C7). Found, %: C 60.63; H 4.65; N 12.91; S 14.60.
C11H10N2OS. Calculated, %: C 60.55; H 4.59; N 12.84;
S 14.68.
2-(1H-Imidazol-2-sulfinyl)-1-phenylethanone (IIb).
Yield 47% (a), 98% (b). White crystals, mp 108°C. IR
1
spectrum, ν, cm-1: 1026 (S=O). H NMR spectrum, δ,
ppm: 5.15 d (1H, C8H2, J 15.5 Hz), 5.20 d (1H, C8H2,
J 15.5 Hz), 7.17 s (1H, C4CH), 7.47 s (1H, C5CH), 7.59 t
(2H, C3AH , C5AH, J 7.5 Hz), 7.73 t (1H, C4AH, J 7.4 Hz),
8.01 d (2H, C2AH, C6AH, J 7.7 Hz), 13.44 s (1H, N1CH).
13C NMR spectrum, δ, ppm: 62.04 (C8), 121.78 (C5C),
129.08 (C3A, C5A), 129.37 (C4C, C2A, C6A), 134.65 (C4A),
136.08 (C1A), 146.64 (C2C), 193.01 (C7). Found, %:
C 56.45; H 4.32; N 12.03; S 13.71. C11H10N2O2S. Cal-
culated, %: C 56.41; H 4.27; N 11.96; S 13.67.
2-(2-Hydroxyethylsulfanyl)-1-phenylethanone (Ic).
Yield 49–60%. Brown oily fluid, bp 134°C. IR spectrum,
1
ν, cm–1: 1672 (C=O), 690 (C–S). H NMR spectrum,
δ, ppm: 2.78 t (2H, C1H2, J 5.8 Hz), 3.77 t (2H, C2H2,
J 5.9 Hz), 3.89 s (2H, C8H2), 7.48 t (2H, C3AH, C5AH,
J 7.3 Hz), 7.59 t (1H, C4AH, J 7.3 Hz), 7.96 d (2H, C2AH,
C6AH, J 7.2 Hz). 13C NMR spectrum, δ, ppm: 35.42
(C1), 37.13 (C8), 60.70 (C2), 128.76 (C2A, C3A, C5A,
C6A), 133.62 (C4A), 135.14 (C1A), 195.14 (C7). Found,
%: C 61.18; H 6.17; S 16.30. C10H12O2S. Calculated, %:
C 61.22; H 6.12; S 16.33.
2-(2-Hydroxyethylsulfinyl)-1-phenylethanone (IIc).
Yield 53% (a), 54% (b). White crystals, mp 106°C. IR
1
spectrum, ν, cm–1: 1028 (S=O). H NMR spectrum, δ,
ppm: 3.04 m (2H, C1H2), 3.84 m (2H, C2H2), 4.66 d (1H,
C8H2, J 15.5 Hz), 4.70 d (1H, C8H2, J 15.5 Hz), 7.59 t (2H,
C3AH, C5AH, J 7.5 Hz), 7.72 t (1H, C4H, J 7.4 Hz), 8.03 d
(2H, C2AH, C6AH, J 7.5 Hz). 13C NMR spectrum, δ, ppm:
54.30 (C1), 55.15 (C2), 60.72 (C8), 129.19 (C3A, C5A),
129.30 (C2A, C6A), 134.48 (C4A), 136.60 (C1A), 194.04
(C7). Found, %: C 56.67; H 5.71; S 15.12. C10H12O3S.
Calculated, %: C 56.60; H 5.66; S 15.09.
Oxidationofβ-ketosulfidesIa–Ictoβ-ketosulfoxides.
General procedure. a. To s solution of 0.232 g (1 mmol)
of compound Ia–Ic in 10 ml of CH2Cl2 was added at
stirring 0.173 g (1 mmol) of m-chloroperbenzoic acid
at 20°C within 1 h. The sulfoxide was extracted with
tert-butyl methyl ether, the extract was washed with
saturated Na2CO3 solution, with brine and water, dried
with Na2SO4. The solvent was evaporated, the reaction
products were isolated by chromatography.
2-(5-Chloro-1-methyl-1H-imidazol-2-ylsulfanyl)-
1-phenylethanone (III). Yield 47%. Yellow crystals,
mp 82–83°C. IR spectrum, ν, cm–1: 1680 (C=O), 804
1
(C–Cl), 690 (C–S). H NMR spectrum, δ, ppm: 3.53 s
(3H, C6CH3), 4.68 s (2H, C8H2), 7.04 s (1H, C4CH), 7.55 t
(2H, C3AH, C5AH, J 7.6 Hz), 7.69 t (1H, C4AH, J 7.2 Hz),
7.98 d (2H, C2AH, C6AH, J 7.7 Hz). 13C NMR spectrum, δ,
ppm: 31.51 (C6C), 41.38 (C8), 126.21 (C5C), 128.90 (C4C,
C3A, C5A), 129.23 (C2A, C6A), 134.11 (C4A), 135.71 (C1A),
140.03 (C2C), 194.28 (C7). MaCC-Cпeqtp, m/z (IOtH., %):
b. To a solution of 0.116 g (0.5 mmol) of compound
Ia–Ic in 10 ml of CH2Cl2 was added at stirring 11 ml (0.5
mmol) of ClO2 solution in CH2Cl2 at 20°C within 30 min.
The sulfoxide was extracted with tert-butyl methyl ether,
the extract was washed with saturated Na2CO3 solution,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 2 2013

SYNTHESIS OF POLYFUNCTIONAL β-KETOSULFIDES
207
268 (10.5) [M + 2]+, 266 (27.5) [M]+. Found, %: C 54.09;
REFERENCES
H 4.11; Cl 13.32; N 10.54; S 11.94. C12H11ClN2OS. Cal-
culated, %: C 54.03; H 4.13; Cl 13.31; N 10.51; S 12.01.
M 266.7.
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ACKNOWLEDGMENTS
3. Comprehensive Organic Chemistry, Barton, D. and Ol-
The study was carried out under a financial support
of the Ural Division of the RussianAcademy of Sciences
(project no.12-M-35-2055).
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4. Loginova, I.V., Ashikhmina, E.V., Rubtsova, S.A., Krym-
skaya, Yu.V., and Kuchin, A.V., Zh. Org. Khim., 2008,
vol. 44, p. 1799.
The authors express their gratitude to the researchers
of the laboratory of the physicochemical investigation
method of the Institute of Chemistry of Komi Scientific
Center for registering NMR and IR spectra.
5. Loginova, I.V., Rodygin, K.S., Rubtsova, S.A., Slepukh-
in, P.A., Kuchin, A.V., Polukeev, V.A., Zh. Org. Khim.,
2011, vol. 47, p. 125.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 2 2013