Reactions of 2-diazo-1,3-dicarbonyl compounds with aromatic thioketones (superdipolarophiles)

Full text of DOI:10.1134/S107042801112027X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 12, pp. 1911–1913. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.A. Nikolaev, A.V. Ivanov, A.A. Shakhmin, B. Schulze, L.L. Rodina, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 12, pp. 1873–1875.
SHORT
COMMUNICATIONS
Reactions of 2-Diazo-1,3-dicarbonyl Compounds with Aromatic
Thioketones (Superdipolarophiles)
V. A. Nikolaeva, A. V. Ivanova, A. A. Shakhmina, B. Schulzeb, and L. L. Rodinaa
a St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: vnikola@VN6646.spb.edu
b Universität Leipzig, Leipzig, Germany
Received July 6, 2011
DOI: 10.1134/S107042801112027X
Cycloaddition reactions of aliphatic diazo com-
pounds are widely used in the synthesis of various
nitrogen-containing and other heterocycles [1–3]. In
these reactions, the most reactive dipoles are believed
to be diazoalkanes and 2-diazo ketones, whereas cyclo-
addition of 2-diazo-1,3-dicarbonyl compounds to com-
mon dipolarophiles is not typical [2, 3].
The goal of the present work was to study cyclo-
addition of 2-diazo-1,3-dicarbonyl compounds to
“superdipolarophiles” [4], i.e., aromatic thioketones
which exhibit the highest reactivity in cycloaddition
processes, and elucidate the possibility for synthesiz-
ing in such a way O- and S-containing heterocycles.
As substrates we used acyclic and carbocyclic
2-diazo-1,3-dicarbonyl compounds, diazoacetylacetone
(Ia), ethyl diazoacetoacetate (Ib), and diazodimedone
(Ic), and thiobenzophenone (II), thiofluorenone, and
other aromatic thioketones were selected as dipolaro-
philes. We have found that diazodicarbonyl com-
pounds Ia–Ic react with aromatic thioketones even at
room temperature to give tetrasubstituted 1,3-oxa-
thioles IIIa–IIIc as final products (Scheme 1).
they can be stored for a long time without appreciable
decomposition, we presumed that the reaction follows
a conventional three-step scheme which was proposed
for analogous processes with participation of diazo
ketones and other diazomonocarbonyl compounds
[5, 6]. Initially, [3+2]-cycloaddition of dipolar diazo
group at the C=S bond of thioketone gives unstable
thiadiazoles IV which lose nitrogen molecule to gen-
erate reactive thiocarbonyl ylides V; the latter undergo
intramolecular 1,5-electrocyclization leading to
1,3-oxathioles III.
Cyclization of C=S ylide V generated from unsym-
metrically substituted diazodicarbonyl compounds
could produce two regioisomeric oxathioles. However,
in the reaction with diazo ester Ib, electrocyclization
of the corresponding ylide occurs chemoselectively at
the acetyl group, whereas the ester fragment remains
intact, and the product is only one regioisomer,
1,3-oxathiole IIIb. Cyclic diazodiketone Ic reacted
with thioketones at a much lower rate, and elevated
temperature was necessary to accelerate the process.
As a result, the reaction was accompanied by partial
decomposition of diazodimedone (Ic) with formation
of the Wolff rearrangement product, 2-oxoketene. The
Taking into account that diazodicarbonyl com-
pounds Ia–Ic are stable under usual conditions and that
Scheme 1.
R
R'
R
R'
R
R'
R
R'
S
18–25°C
O
O
O
O
O
O
+
N
S
O
O
–N2
S
Ph
Ph
S
Ph
Ph
N
N2
Ph
Ph
IIIa–IIIc
Ph
Ph
Ia–Ic
II
IV
V
I, R = R′ = Me (a); R = MeO, R′ = Me (b); RR′ = CH2C(Me)2CH2 (c).
1911

NIKOLAEV et al.
1912
Scheme 2.
O
O
O
Me
Me
S
II, 80°C
Me
Me
Ph
Ph
S
+
–N2
Me
Ph
O
O
O
Me
Ph
N2
Ic
IIIc
VI
latter reacted with thioketone present in the reaction
mixture to give [4+2]-cycloaddition product, oxathi-
inone VI, the ratio IIIc–VI being ~2.2:1 (Scheme 2).
Methyl 5-methyl-2,2-diphenyl-1,3-oxathiole-
4-carboxylate (IIIb). Benzene, 10 ml, was added to
793 mg (4 mmol) of freshly prepared thiobenzo-
phenone, the mixture was heated to 90–95°C, a part of
the solvent (~5 ml) was distilled off to remove traces
of water, the mixture was cooled to room temperature,
a few grains of anhydrous calcium chloride were
added, 640 mg (4.5 mmol) of methyl 2-diazo-3-oxo-
butanoate (Ib) was added, and the flask was flushed
with argon, hermetically capped, and kept for 63 days
at 18–25°C. After 2 months, the yield of oxathiole IIIb
was 61% (74% on the reacted diazo ester Ib) accord-
As in reactions with diazoalkanes and diazoketones
[4–6], the most reactive aromatic thioketones toward
diazodicarbonyl compounds Ia–Ic were thiobenzo-
phenone and thiofluorenone. The structure of oxa-
thioles IIIa–IIIc and oxathiinone VI was reliably
determined by spectral methods.
Thus we have shown that relatively inert (in cyclo-
addition reactions) 2-diazo-1,3-dicarbonyl compounds
react with thioketones to give tetrasubstituted 1,3-oxa-
thioles. Reactions of cyclic diazodiketones with thio-
ketones at elevated temperature are accompanied by
Wolff rearrangement of the initial diazodiketone and
subsequent [4+2]-cycloaddition of 2-oxoketene at the
C=S bond.
1
ing to the H NMR data. The solvent was distilled off
under reduced pressure (15–20 mm), the residue
(1.24 g) was applied onto 2.5 g of silica gel and
transferred to a column charged with 25 g of silica gel
(Woelm Pharma). The column was eluted with petro-
leum ether–tert-butyl methyl ether (1:0 to 10:1). Yield
442 mg (35%, 43% on the reacted diazo ester Ib),
Rf 0.42 (petroleum ether–tert-butyl methyl ether, 3:1),
1-(5-Methyl-2,2-diphenyl-1,3-oxathiol-4-yl)-
ethanone (IIIa). A mixture of 785 mg (3.96 mmol) of
diphenylmethanethione (II) and 500 mg (3.97 mmol)
of ethyl 3-diazopentane-2,4-dione in 5 ml of benzene
was left to stand for several days at 18–20°C under
1
mp 72–73°C (from petroleum ether). H NMR spec-
trum, δ, ppm: 2.38 s (3H, 5-CH), 3.72 s (3H, OCH3),
7.38–7.29 m (6H, Harom), 7.52–7.44 m (4H, Harom).
13C NMR spectrum, δC, ppm: 14.9 (5-CH3), 51.9
(OCH3); 102.0 and 101.3 (C4, C2); 126.5, 128.3, 128.6,
143.1 (Carom); 158.6 (C5), 163.7 (C=O). Found, %:
C 69.39, 69.45; H 5.34, 5.44. C18H16O3S. Calculated,
%: C 69.21; H 5.16.
1
nitrogen. According to the H NMR data (using
N-methylmaleimide as reference), the concentration of
oxathiole IIIa in the reaction mixture in 3, 5, and
7 days was 14, 29, and 47%, respectively. After 7 days,
the solvent was distilled off under reduced pressure
(10–12 mm), and the residue was subjected to chro-
matography on silica gel (50 g) using petroleum ether–
diethyl ether (10:1) as eluent. The major fraction was
dried over anhydrous MgSO4 and evaporated. Yield
425 mg (38%; 54% calculated on the reacted diazo-
acetylacetone), oily substance which slowly crystal-
lized on cooling to 0°C, mp 54–56°C (from tert-butyl
methyl ether), Rf 0.45 (petroleum ether–tert-butyl
Reaction of 2-diazo-5,5-dimethylcyclohexane-
1,3-dione (Ic) with thiobenzophenone (II) at 80°C.
A mixture of 1.0 g (6 mmol) of compound Ic and
1.19 g (6 mmol) of thioketone II in 10 ml of benzene
was heated for 4 days under reflux. The solvent was
distilled off under reduced pressure (10–12 mm) at
1
40°C. According to the H NMR data, the crystalline
residue (1.9 g) contained 0.256 g (13%) of oxathiinone
VI and 0.553 g (28%) of oxathiole IIIc. The product
mixture was separated by column chromatography on
silica gel (50 g) using hexane–diethyl ether as eluent
(gradient mode); in order of elution, 113 mg of com-
pound VI and 502 mg of IIIc were isolated.
1
methyl ether, 2:1). H NMR spectrum, δ, ppm: 2.26 s
(3H, 5-CH3), 2.38 s (3H, COCH3), 7.39–7.28 m (6H,
Harom), 7.54–7.46 m (4H, Harom). 13C NMR spectrum,
δC, ppm: 15.7 (5-CH3), 30.5 (COCH3), 101.1 (C2),
112.6 (C4); 126.4, 128.2, 128.5, 142.9 (Carom); 157.1
(C5), 191.3 (C=O). Mass spectrum (ESI): m/z 297
[M + H]+.
6,6-Dimethyl-2,2-diphenyl-4,5,6,7-tetrahydrocy-
clopenta[e][1,3]oxathiin-4-one (VI). Yield 113 mg
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 12 2011

REACTIONS OF 2-DIAZO-1,3-DICARBONYL COMPOUNDS
1913
(6%), mp 112–113°C, Rf 0.57 (diethyl ether–hexane,
1:1). H NMR spectrum, δ, ppm: 0.98 s (6H, CH3),
from the corresponding ketones according to known
procedures [8, 9].
1
2.29 s (2H, 7-H), 2.46 s (2H, 5-H), 7.54–7.33 m (10H,
The authors thank DAAD and Institute of Organic
Chemistry (Leipzig University, Germany) for financial
support of the present study.
H
arom). 13C NMR spectrum, δC, ppm: 29.4 (C6), 34.7
(CH3), 48.6 and 42.0 (C5, C7), 98.4 (C2), 114.2
(C4a); 127.2, 128.4, 129.0, 141.4 (Carom); 171.4 (C7a),
181.5 (C4).
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6,6-Dimethyl-2,2-diphenyl-4,5,6,7-tetrahydro-
1,3-benzoxathiol-4-one (IIIc). Yield 237 mg (13%),
Rf 0.50 (petroleum ether–tert-butyl methyl ether, 2:1),
colorless crystals, mp 157–158°C (from tert-butyl
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 12 2011