1742
Can. J. Chem. Vol. 83, 2005
Fig. 1. Odorless cyclic ketene dithioacetals.
Scheme 1. Thioacetalization of carbonyl compounds 2 with 1c.
O
O
O
MeCOCl
MeOH
OH
S
S
+
S
S
R1
R2
R1
R2
2
1c
3
creased by 25% when the reaction of thermo- and acid-
sensitive furan-2-carbaldehyde (2l) proceeded at room tem-
perature rather than at reflux. Generally, it is difficult to
cleanly realize the thioacetalization of 2l with the use of
conventional acid catalysts (12). Several research groups re-
ported high-yield thioacetalizations of 2l by using thionyl
chloride treated silica gel (12), trimethylsilyl chloride (13),
and lithium tetrafluoroborate (14) as the catalyst, respec-
tively. Our thioacetalization of 2l can be considered a useful
alternative procedure.
In contrast with 2a–2p, the aromatic ketones 2q–2u could
not be thioacetalized at room temperature, but they gave
their corresponding dithioacetals in high yields after pro-
longed reflux. The aromatic sterically hindered benzophe-
none (Table 1, entry 37) was the slowest to react with an
excess of 1c (feed molar ratio of acetyl chloride : 1c : 2 =
3:4:2).
To exploit the differences in the thioacetalization rate of
aldehydes and aliphatic ketones and aromatic ketones, for
the selective protections we carried out some competitive re-
actions under the above reaction conditions (Table 1, entries
38 and 39). The reaction of 2b–2q–1c with a 1:1:1 molar ra-
tio performed at reflux temperature (Table 1, entry 38) af-
forded the thioacetal 3b in 92.4% yield, while the ketone 2q
was almost completely recovered (97.2%), 3q not even be-
ing detectable. Similar results were obtained in the case of
2p–2q–1c with a 1:1:1 molar ratio (Table 1, entry 39), where
2p was converted into thioacetal 3p in 91.2% yield, while 2q
remained intact. The reported thioacetalization procedure
thus showed a high chemoselectivity, providing selective
protection of an aromatic aldehyde or an aliphatic ketone in
the presence of an aromatic ketone.
The mechanism of the thioacetalization reaction was in-
vestigated with the help of a supporting reaction. The mix-
ture of 1c (1.0 mmol), 2a (1.0 mmol), and acetyl chloride
(1.5 mmol) in methanol (10 mL) was stirred at room temper-
ature and interrupted after 50 min by neutralizing with 10%
aq. NaHCO3. With this procedure, decarboxylated product
1-(1,3-dithian-2-ylidene)propan-2-one (4) and dithioacetal
3a were obtained in 79.3% and 14.6% yields, respectively,
while unreacted 2a (81.3%) was recovered. Compound 4
was also obtained in our previous work and assumed to be
an intermediate (7a, 7b). These results indicate that 1c un-
dergoes decarboxylation much more easily than deacylation
under the acidic conditions applied. The novelty of the re-
agent 1c is in the fact that the thioacetalization of aldehydes
and aliphatic ketones could proceed at room temperature
with high yields. On the basis of the previously mentioned
experimental results together with our previous work (7), a
mechanism for the thioacetalization reaction of various car-
bonyl compounds with 1c in methanol is proposed in
EtOH–H2O, affording the same intermediate obtainable with
1b (9a). With the aim of obtaining efficient and practical re-
agents for general application, we investigated the
thioacetalization reaction of a range of selected carbonyl
compounds 2 with 1c.
Results and discussion
According to the literature, we prepared ethyl 2-(1,3-
dithian-2-ylidene)-3-oxobutanoate (10) from ethyl 3-
oxobutanoate, carbon disulfide, 1,3-dibromopropane, and
K2CO3 in nearly quantitative yield (99%), then we converted
it into the 2-(1,3-dithian-2-ylidene)-3-oxobutanoic acid (1c)
via a hydrolysis process (9a, 11). It is worth noting that 1c is
an odorless solid, stable under ambient atmosphere, which is
associated with some advantages such as a simple synthetic
procedure, mild conditions, high yield, and commercial
starting materials without a foul smell.
Since our previous experience has revealed that it is a con-
venient way to achieve the thioacetalization of a range of al-
dehydes and ketones in the presence of a mixture of acetyl
chloride and methanol (7b), in the present work the same
mixture was adopted for studying the thioacetalization of
various carbonyl compounds 2 with 1c (Scheme 1).
The thioacetalization of piperonal (2a) with 1c, initially
carried out under reflux, showed that the reaction was com-
pleted within 30 min affording the corresponding dithio-
acetal 3a in 89.3% yield. Significantly, this reaction
proceeded much faster in comparison to the reaction re-
ported in our previous work (7). So, we repeated the reaction
at room temperature. To our delight, 2a was transformed
into 3a in 92.7% yield within 2 h. It is worth mentioning
that only a very faint smell of thiol was perceived during
both the reaction and work-up process, in agreement with
practically no release of 1,3-propanedithiol.
We next investigated the thioacetalization of aromatic,
aliphatic, and heterocyclic aldehydes and ketones (2a–2w)
with 1c in the presence of acetyl chloride in methanol at
both room and reflux temperatures. With a constant feed
molar ratio of acetyl chloride : 1c : 2 of 3:2:2, all the reac-
tions proceeded smoothly under mild acidic conditions. Ta-
ble 1 summarizes some reaction data. The results confirm
the general value of 1c as a key reagent for the thioacetali-
zation reaction.
A range of aromatic and aliphatic aldehydes and aliphatic
ketones (2a–2p) were rapidly converted into their corre-
sponding dithioacetals (3a–3p) in very high yields at both
room and reflux temperatures. The reflux condition allowed
a shorter reaction time, nevertheless, some thermosensitive
substrates could benefit from the use of room temperature.
In the cases of entries 23 and 24 in Table 1, the yield was in-
© 2005 NRC Canada