DBSA-catalyzed hydrolysis of chain α-oxo ketene dithioacetals in water: Aqueous synthesis of β-ketothioesters

Article abstract of DOI:10.1080/00397911.2017.1368084

In this paper, we wish to report an environment friendly synthetic method for β-ketothioesters from a dodecylbenzenesulfonic acid (DBSA)-catalyzed hydrolysis reaction of chain α-oxo ketene dithioacetals in water. It was shown that the hydrolysis reaction of chain α-oxo ketene dithioacetals could efficiently occur in the presence of 7.5 mol% DBSA at 100 °C in water, affording the desired β-keto thioesters in excellent yields.

Full text of DOI:10.1080/00397911.2017.1368084

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
DBSA-catalyzed hydrolysis of chain α-oxo ketene
dithioacetals in water: Aqueous synthesis of β-
ketothioesters
Fei Qi, Hai-Feng Yu, Yue-Nan Wang, Ye Lv, Ya-Xi Li, Lu Han, Rong Wang & Xi-
Ning Feng
To cite this article: Fei Qi, Hai-Feng Yu, Yue-Nan Wang, Ye Lv, Ya-Xi Li, Lu Han,
Rong Wang & Xi-Ning Feng (2017): DBSA-catalyzed hydrolysis of chain α-oxo ketene
dithioacetals in water: Aqueous synthesis of β-ketothioesters, Synthetic Communications, DOI:
10.1080/00397911.2017.1368084
To link to this article: http://dx.doi.org/10.1080/00397911.2017.1368084
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Date: 29 August 2017, At: 05:35

DBSA-catalyzed hydrolysis of chain -oxo ketene
dithioacetals in water: Aqueous synthesis of-ketothioesters
Fei Qi
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Hai-Feng Yu*
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Yue-Nan Wang
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Ye Lv
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Ya-Xi Li
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Lu Han
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Rong Wang
1

School of Chemistry and Life Science, Anshan Normal University, Anshan, China
Xi-Ning Feng
School of Chemistry and Life Science, Anshan Normal University, Anshan, China
*Address correspondence to Hai-Feng Yu, School of Chemistry and Life Science, Anshan
Normal University, Anshan, Liaoning 114007, China. E-mail: yuhf68105@sina.com
Supported by Funds for College Students’ innovation and entrepreneurship training project of
Liaoning Province (201610169005), Natural Science Foundation of Liaoning Province
(201602002).
ABSTRACT
In this paper, we wish to report an environment friendly synthetic method for
-ketothioesters from a dodecylbenzenesulfonic acid (DBSA)-catalyzed hydrolysis reaction of
chain -oxo ketene dithioacetals in water. It was shown that the hydrolysis reaction of chain
-oxo ketene dithioacetals could efficiently occur in the presence of 7.5 mol% DBSA at 100°C
in water, affording the desired -keto thioesters in excellent yields.
GRAPHICAL ABSTRACT
KEYWORDS: dodecylbenzenesulfonic acid, hydrolysis reaction, ketene dithioacetal, thioester
2

Introduction
Over the past decades, -xo ketene dithioacetals, which are easily available and stable,
had been regarded as versatile and significant synthons in organic synthesis due to their unique
structural characters and reactivity.[1–5] -Ketothioesters as an important subset of carboxylic acid
derivatives had been utilized as versatile synthetic intermediates for further elaboration of
thioesters and the synthesis of a range of potent natural products.[6] As a result, in the past
decades, much effort has focused on the synthesis of -ketothioesters,[7] including the
mercaptolysis of diketene,[7a] 2,2,6-trimethyl-4 H-1,3–dioxin-4-one[7b] or acylatedmeldrum’s
acids,[7c] and the aldol reaction between aldehydes and S-ethyl acetothioate followed by
oxidation with the Dess-Martin periodinane.[7d] Recently, we reported one-pot synthesis of
-alkylated
-ketothioesters
by
FeCl3·6H2O-catalyzed
tandem
Friedel-Crafts
alkylation/hydrolsis reaction between chain -oxoketene dithioacetals and alcohols.[8] However,
all the reported reactions are performed in organic medium such as acetonitrile and
dichloromethane, which can lead to serious environmental and safety problems. Therefore, from
the green chemistry point of view, the development of environmental compliant synthetic method
for -ketothioesters remains imperative.
Organic reaction in water without the use of organic solvents was recently received
considerable attention in green chemistry because the use of water can remarkably reduce the
discharge of harmful organic solvents.[9]In recent years, we have been interested in the organic
3

reaction of -oxoketene dithioacetals in water,[10] and reported dodecylbenzenesulfonic acid
(DBSA) efficiently catalyzed thioacetalization[10a] and synthesis of dithianes[10b] utilizing ketene
dithioacetals as odorless thiol equivalent as well as Friedel-Crafts alkylation of cyclic ketene
dithioacetals with alcohols in water.[10c] As part of our continuing research in the context, we more
recently investigated DBSA-catalyzed hydrolysis of chain -oxo ketene dithioacetals in water to
gain an environmental compliant synthetic method for -ketothioesters. Herein, we would like to
report our finding.
Results and Discussion
According to our previous work,[10] we selected a surfactant-type Brønsted acid DBSA as
catalyst to investigate the hydrolysis of chain -oxo ketene dithioacetals in water. The hydrolysis
of 3, 3-bis (ethylthio)-1-phenylprop-2-en-1-one 1a (0.5 mmol) was selected as a model reaction
to screen the catalyst loading and reaction temperature. The results are summarized in Table 1.
Apparently, the catalyst loading and reaction temperature have a dramatic influence on this
reaction. We initially examined the reactions in the presence of various catalysts loading in water
at reflux (Table 1, entries 1-6), and found that using 7.5 mol% DBSA, the reaction efficiently
afford the desired product S-ethyl-oxo-3-phenyl propane thioate 2a in excellent yields (Table 1,
entry 5). However, on changing the amount of DBSA from 7.5 mol % to 5 mol %, the reaction
less efficiently carried out even prolonging reaction time (Table 1, entries 6 and 7). With this,
we selected 7.5mol % of DBSA as catalyst. It is noteworthy that the obtained 2a was
4

indissociable mixture of enol and keto isomers, reaching the keto/enol ratio of 5:4 determined by 1H
NMR. Next, we tested the influence of reaction temperature in the presence of 7.5mol % of
DBSA, and found the reaction proceeded less efficiently below 100oC (Table 1, entries 8 and 9).
Accordingly, the optimal reaction conditions are 7.5mol % of DBSA as catalyst and at 100 oC.
Next, we investigated the scope of the reaction under the optimal reaction conditions. The
results are summarized in Table 2. Initially, we checked the hydrolysis of -oxo ketene
diethylthioacetals
such
as
3,3-bis(ethylthio)-1-arylprop-2-en-1-one,
4,4-bis(ethylthio)but-3-en-2-one and (E)-1,1-bis(ethylthio)-5-(p-tolyl)penta-1,4-dien -3-one. It
was found that these reactions proceeded smoothly to give corresponding -ketothioesters 2a-k
in excellent yields, and obviously the electronic effects of electron-donating and
electron-withdrawing groups on the aromatic rings in3,3-bis(ethylthio)-1-aryl-prop-2-en-1-one
are insignificant to the hydrolysis reaction. It was worth noting that 3,
3-bis(ethylthio)-1-(furan-2-yl)prop-2-en-1-onebearing thermo-and acid-sensitive furyl preformed
similar reaction to furnish S-ethyl 3-oxo-3-(thiophen-2-yl)propane thioate 2h in 84% yield.
Later, in
a
similar fashion, we tested the hydrolysis of
a
variety of 3,
S-alkyl
3-bis(alkylthio)-1-phenylprop-2-en-1-one,
and
corresponding
3-oxo-3-phenylpropanethioate 2l-o were obtained in excellent yields. The products 2 were
1
always obtained as the mixture of keto/enol isomers, and their molar ratio was determined by H
NMR. In general, the keto isomers of 2 are in preference to their enol isomers, compound 2i
5

reaching the highest keto/enol ratio of 5:1. However, the enol isomer of (E)-S-ethyl
3-oxo-5-phenyl pent-4-ene thioate 2k is major due to its stable conjugation structure.
On the basis of our previous work[10] and the obtained results, a possible reaction
mechanism was proposed in Scheme 1.
It is clear that the reaction commenced from the formation of the carbocation I by the
combination of -oxo ketene dithioacetals 1 with H+. Then, nucleophilic attack at the cationic
carbon atom of I by H2O forms the intermediate II, which converted into the intermediate III
after the removal of thiol. Finally, the elimination of H + of intermediate III occurs to afford the
desired products 2. The released H + further completes the catalytic cycle.
In summary, very first time we have successfully developed an environmentally friendly
method for the synthesis of -ketothioesters 2 by DBSA catalyzed hydrolysis reaction of chain
-oxo ketene dithioacetals in water. Further application of the synthesized -ketothioesters is
ongoing in our group.
EXPERIMENTAL
General considerations
1
13
A H and C{1H} NMR spectra were recorded on a Bruker DRX-600 spectrometer and
the chemical shift values refer to  TMS = 0.00 ppm, CDCl3 ( (1H), 7.26 ppm;  (13C), 77.16
ppm) or DMSO-d6 ((1H), 2.5 ppm;  (13C), 39.51 ppm). The HRMS analysis was achieved on
6

Bruck micro Tof by using ESI method. All the melting points were uncorrected. Analytical TLC
plates, Sigma-Aldrich silica gel 60F200 were viewed by UV light (254 nm). Chromatographic
purifications were performed on SDZF silica gel 160.
Typical procedure for the preparation of -ketothioester2
A mixture of chain -oxo ketene dithioacetals 1 (0.5 mmol), DBSA (12.2 mg,
0.0375mmol) and H2O (1 mL) were stirred in 100oC until the complete conversion of 1 as
evidenced by TLC. After completion, water (20 mL) was added to the reaction mixture and
extracted with CH2Cl2 (315 mL). Then, the combined organic phases were dried over
anhydrous MgSO4, filtered, and evaporated under reduced pressure. The resultant residue was
purified by silica gel column chromatography (petroleum ether (30–60oC)/diethyl ether 50:1,
v/v) to give pure 2 as slight yellow oil in excellent yields.
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8

Table 1. Screening of the reaction conditionsa
Entry
DBSA(mol%)
T(oC)
100
100
100
100
100
100
100
90
Time (h)
20
Yield (%)b
1
2
3
4
5
6
7
8
9
0
30
20
10
7.5
5
0
14
94
95
95
96
80
82
84
85
14
15
16
20
5
30
7.5
7.5
16
90
20
aReagents and conditions: 1a (0.5 mmol), H2O solvent (1 mL). bIsolated yield.
9

Table 2. Synthesis of -ketothioesters 2
Reaction condition: 1 (0.5 mmol), DBSA (7.5 mol%), H2O (1 mL), 100oC, 16 h; Isolated yields; keto/enol ratio of 2 determined by
1H NMR.
10

Scheme 1. Plausible Mechanism for the hydrolysis of 1.
11