Reaction of 1,3-dihalopropan-2-ones with 2-sulfanylbenzoic acid mono- and disodium salts

Full text of DOI:10.1134/S1070428011030250

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 3, pp. 461–463. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.A. Tokareva, L.G. Shagun, I.A. Dorofeev, V.A. Shagun, M.G. Voronkov, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 3, pp. 385–387.
SHORT
COMMUNICATIONS
Reaction of 1,3-Dihalopropan-2-ones with 2-Sulfanylbenzoic
Acid Mono- and Disodium Salts
I. A. Tokareva, L. G. Shagun, I. A. Dorofeev, V. A. Shagun, and M. G. Voronkov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: shag@irioch.irk.ru
Received February 26, 2010
DOI: 10.1134/S1070428011030250
Well known biological activity of benzoic acid
derivatives [1] prompted us to examine the possibility
for building up novel heterocyclic systems by reactions
of 2-sulfanylbenzoic acid mono- and disodium salts
with α,α′-dihalo ketones of the general formula
XCH2C(=O)CH2X (Ia–Ic, X = Cl, Br, I). Initial
sodium 2-sulfanylbenzoate (II) was prepared in situ
according to the procedure described in [2] and was
brought into reaction with 1,3-dichloropropan-2-one
(Ia) in aqueous acetone at room temperature. The reac-
tion occurred as intermolecular O-alkylation of sodium
2-sulfanylbenzoate (II) (Williamson reaction [3]) and
led to the formation of 76% of previously unknown
2-oxo-3-(2-sulfanylbenzoyloxy)propyl 2-sulfanylben-
zoate (III) (Scheme 1). The structure of compound III
was confirmed by its elemental composition and IR
and NMR spectra. The IR spectrum of III contained
absorption bands belonging to stretching vibrations of
S–H (2567 cm–1), ester carbonyl (1690 cm–1), and
ketone carbonyl groups (1723 cm–1). Two methylene
units in molecule III gave rise to signals at δ 5.38 ppm
1
in the H NMR spectrum and at δC 67.58 ppm in the
13C NMR spectrum.
In order to construct a heterocyclic system, bis-
benzoate III was treated with 1,3-dihalopropan-2-ones
Ia–Ic with a view to obtain S-alkylation products.
However, these reactions resulted in the formation of
sulfur-containing oligomers which were insoluble in
organic solvents. We succeeded in synthesizing the
desired monomeric cyclization product, compound V,
only by reaction of disodium salt IV with dihalo ke-
tones Ia–Ic (Scheme 2). Macrocyclic 5H,7H,11H,17H-
dibenzo[g,n][1,5,9,13]dioxadithiacyclohexadecine-
5,8,11,18(9H,19H)-tetraone (V) was formed in 63%
Scheme 1.
O
O
O
O
ONa
O
O
Cl
Cl
+
2
O
SH
SH
HS
Ia
II
III
Scheme 2.
O
O
O
O
4
1
12
15
XCH2C(O)CH2X
2MeONa
MeOH
10
O
6
O
11a
15a
8
4a
7
5
13
14
9
11
3
2
Ia–Ic
O
O
III
–2NaX
20
O
O
16
S
20a
19
SNa
NaS
S
17
18
O
IV
V
X = Cl (a), Br (b), I (c).
461

TOKAREVA et al.
462
yield, and the reactivity of dihalo ketones Ia–Ic
decreased in the series I > Br > Cl.
(C=O, ketone). Found, %: C 56.55; H 3.45; S 17.76.
C17H14O5S2. Calculated, %: C 56.35; H 3.86; S 17.67.
2-Oxo-3-(2-sulfanylbenzoyloxy)propyl 2-sul-
fanylbenzoate disodium salt (IV). A solution of
0.26 g (0.004 mol) of sodium methoxide in methanol
was added dropwise to a solution of 0.9 g of com-
pound III in methanol until neutral reaction. The sol-
vent was removed under reduced pressure. Yield 0.9 g
(90%), white powder, decomposes above 350°C. IR
spectrum, ν, cm–1: 1706 (C=O, ketone), 1680 (C=O,
ester). Found, %: C 49.46; H 3.30; Na 10.50; S 15.21.
C17H12Na2O5S2. Calculated, %: C 50.24; H 2.95;
Na 11.33; S 15.76.
The reaction of 2-sulfanylbenzoic acid disodium
salt (VI) with dihalo ketones Ia–Ic gave 5,1-benzoxa-
thiocine-3,6-dione (VII) (Scheme 3). The structure of
heterocyclic compounds V and VII was confirmed by
the data of elemental analysis, mass spectrometry, and
1
IR and H and 13C NMR spectroscopy. In the IR spec-
tra of compounds V and VII we observed strong ab-
sorption bands due to stretching vibrations of ester
(lactone, 1690 and 1712 cm–1) and ketone carbonyl
groups (1714 and 1748 cm–1), respectively. The
13C NMR spectrum of benzoxathiocinedione VII con-
tained a signal at δC 198.26 ppm, which was assigned
to the lactone carbonyl carbon atom. Its chemical shift
was approximately equal to the average chemical shift
of two carbonyl carbon atoms, SC–C(=O)C–S and
OC–C(=O)C–O (δC 196.41 and 200.21 ppm, respec-
tively) in the spectrum of compound (V).
5H,7H,11H,17H-Dibenzo[g,n][1,5,9,13]dioxadi-
thiacyclohexadecine-5,8,11,18(9H,19H)-tetraone
(V). A solution of 0.28 g (0.002 mol) of 1,3-di-
chloropropan-2-one (Ia) in 0.5 ml of dimethyl sulf-
oxide was added to a solution of 0.9 g (0.002 mol) of
disodium salt IV in 5 ml of DMSO. The mixture
turned yellow–orange and was stirred for 1.5 h (until
the initial ketone disappeared according to the TLC
data) and poured onto finely crushed ice. The precip-
itate was filtered off, dried under reduced pressure, and
purified by reprecipitation from chloroform with
hexane. Yield 0.58 g (63%), white powder, mp 185–
186°C. IR spectrum, ν, cm–1: 1714 (C=O, ketone),
Scheme 3.
O
O
O
Ia–Ic
ONa
SNa
VI
–2NaX
O
S
1
VII
1690 (C=O, ester). H NMR spectrum (CDCl3), δ,
ppm: 4.25 s (4H, CH2S), 5.15 s (4H, CH2O), 7.17–
8.00 m (8H, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 46.57 (CH2S), 66.18 (CH2O), 123.49–140.83
(Carom), 167.58 (C=O, ester), 196.41 (C18=O), 200.21
(C8=O). Found, %: C 57.55; H 3.65; S 15.86. M 392
(by cryoscopy in benzene). C20H16O6S2. Calculated, %:
C 57.69; H 3.85; S 15.38. M 416.
According to the results of B3LYP/6-31G(d,p)
quantum-chemical calculations, the most stable con-
former of V is characterized by almost planar arrange-
ment (within 0.2°) of the heteroatoms in the central
heteroring. Each cis-oriented phenyl ring forms with
that plane a dihedral angle of 128.3°.
2-Sulfanylbenzoic acid disodium salt (VI).
Metallic sodium, 0.9 g (0.038 mol), was added in small
pieces under stirring to a solution of 3.0 g (0.019 mol)
of 2-sulfanylbenzoic acid in 30 ml of anhydrous
ethanol. The mixture was heated for 7 h under reflux
and cooled, and the precipitate was filtered off, washed
with a small amount of cold ethanol, and dried under
reduced pressure. Yield 2.8 g (72%), light yellow
powder, decomposes above 350°C. IR spectrum:
ν 1591 cm–1 (C=O). 1H NMR spectrum (D2O), δ, ppm:
7.15–7.83 m (4H, Harom). 13C NMR spectrum (D2O),
δC, ppm: 121.49–144.23 (Carom), 168.51 (C=O). Found,
%: C 42.69; H 2.38; Na 22.76. C7H4Na2O2S. Calculat-
ed, %: C 42.42; H 2.02; Na 23.23.
2-Oxo-3-(2-sulfanylbenzoyloxy)propyl 2-sul-
fanylbenzoate (III). An aqueous solution of 0.4 g
(0.01 mol) of sodium hydroxide was added dropwise
to a solution of 2 g (0.01 mol) of 2-sulfanylbenzoic
acid in aqueous acetone until the mixture became
neutral. A solution of 0.7 g (0.006 mol) of 1,3-di-
chloropropan-2-one (Ia) in acetone was added to the
resulting solution of salt II at room temperature, and
the mixture was stirred for 2 h until a solid separated.
The precipitate was filtered off, washed with water and
acetone, and dried under reduced pressure. Yield 1.8 g
(76%), white powder, mp 245°C. IR spectrum, ν, cm–1:
2567 (S–H), 1723 (C=O, ketone), 1690 (C=O, ester).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.88 s (2H,
SH), 5.38 s (4H, CH2), 7.27–8.03 m (8H, Harom).
13C NMR spectrum (DMSO-d6), δC, ppm: 67.58 (CH2),
124.80–137.10 (Carom), 161.48 (C=O, ester), 201.15
5,1-Benzoxathiocine-3,6-dione (VII). A solution
of 0.23 g (1.2 mmol) of 2-sulfanylbenzoic acid disodi-
um salt (VI) in 5 ml of DMSO was slowly added to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 3 2011

REACTION OF 1,3-DIHALOPROPAN-2-ONES WITH 2-SULFANYLBENZOIC ACID
463
a solution of 0.15 g (1.2 mmol) of 1,3-dichloropropan-
2-one (Ia) in 3 ml of DMSO. The mixture was kept for
24 h at room temperature (TLC) and poured onto
finely crushed ice, and the precipitate was filtered off,
dried under reduced pressure, and purified by reprecip-
itation from chloroform with hexane. Yield 0.15 g
(62%), off-white powder, mp 105°C. IR spectrum, ν,
cm–1: 1748 (C=O, ketone), 1712 (C=O, lactone).
1H NMR spectrum (DMSO-d6), δ, ppm: 5.24 s (2H,
CH2S), 5.36 s (4H, CH2O), 7.17–8.00 m (4H, Harom).
13C NMR spectrum (DMSO-d6), δC, ppm: 41.35
(CH2S), 67.75 (CH2O), 125.36–139.86 (Carom), 165.15
(C6=O), 198.26 (C3=O). Mass spectrum: m/z 208 [M]+.
Found, %: C 58.10; H 3.65; S 14.95. C10H8O3S. Cal-
culated, %: C 57.69; H 3.85; S 15.38. M 208 (for 32S).
respectively. The IR spectra were measured in KBr on
a Bruker IFS-25 spectrometer. The mass spectra (elec-
tron impact, 70 eV) were obtained on a GCMS-
QP5050A quadrupole instrument with direct sample
admission into the ion source. The purity of the isolat-
ed compounds was checked by thin-layer chromatog-
raphy on Silufol UV-254 plates using chloroform as
eluent.
REFERENCES
1. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Meditsina, 1985, parts 1, 2.
2. Voore, C.E., Ph. D. Dissertation, Wichita, 2007.
3. Mishchenko, G.L. and Vatsuro, K.V., Sinteticheskie
metody organicheskoi khimii (Synthetic Methods in
Organic Chemistry), Moscow: Khimiya, 1982, p. 12.
1
The H and 13C NMR spectra were recorded on
a Bruker DPX-400 instrument at 400 and 100 MHz,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 3 2011