Two birds with one stone
47
sequence, if one reactant was mixed with another in one
portion (either neat or in solution), the mixture turned
brown rapidly and was accompanied by apparent exother-
micity. When aldehyde in ethanol was added dropwise to
an alcoholic solution of aminothiophenol, the cyclization
proceeded smoothly and no by-products could be detected
by TLC. In comparison, the second step of the reaction is
insensitive to feed-in fashion; therefore, 1,4-benzoquinone
could be added in one portion. An attempt to add three
starting materials (aldehyde, aminothiophenol, and benzo-
quinone) in one portion failed completely. Only traces of
the expected products were found, along with large
amounts of by-products.
viewpoint of atom economy [17], co-production processes
would be highly beneficial. When our procedure was
employed, in the case of 2-phenylbenzothiazole and hydro-
quinone synthesis (Table 1, entry 1), the theoretical atom
economy was calculated as 95%. Only one water molecule
was eliminated during the imine formation step, and the
hydrogen transfer step has 100% atom economy.
The ease of separation of the two products is an
important issue in evaluating a potential co-production
process. In our procedure, the two products could be
readily separated by water dilution. Hydroquinone was
isolated from 2-arylbenzothiazoles due to its excellent
solubility in aqueous ethanol (50 wt%). In contrast, at
room temperature, the solubility of 2-arylbenzothiazoles in
aqueous ethanol (50 wt%) is very poor.
Recently, the application of Hantzsch 1,4-dihydropyri-
dine as reductant (hydrogen donor) has been a hot topic in
organic synthesis [15]. In many cases where Hantzsch
1,4-dihydropyridine and other NAD(P)H analogues such as
1-benzyl-1,4-dihydronicotinamide [16] were used, it was
emphasized that the transfer hydrogenation reactions were
performed under an argon or nitrogen atmosphere. To
explore the effect of atmosphere on our reaction couple,
control experiments were conducted under both an ambient
and a nitrogen atmosphere. It is worth noting that, at the
end of the first step of the reaction, a small amount of
2-arylbenzothiazole could be detected along with 2-aryl-2,
3-dihydrobenzothiazole, perhaps due to the aerobic oxidation
of the desired compound under an ambient atmosphere.
Hence, protection from oxygen is necessary for higher final
yields.
In summary, a novel and practical approach to 2-aryl-
benzothiazoles and hydroquinone was developed based on
the redox co-production strategy. The waste stream mini-
mization, operational simplicity, good energy efficiency,
atom economy, excellent yields, and the straightforward
nature of the reaction procedure make it a very useful
addition to the toolbox of organic chemists and chemical
engineers.
Experimental
All products are known compounds; their physical and
spectroscopic data were compared with those reported in
the literature [18–21] and found to be identical. Melting
points were measured on a Bu¨chi B-540 apparatus. IR
spectra were recorded on a Nicolet Nexus 470 spectro-
photometer in KBr pellets. 1H NMR spectra were recorded
on a Bruker AV 400 spectrometer in CDCl3 with TMS as
internal standard.
After optimizing the abovementioned reaction condi-
tions, the following protocol was subsequently used.
Aromatic aldehydes were treated with 2-aminothiophenol
(1 equiv.) followed by 1,4-benzoquinone (1 equiv.) at
room temperature in ethanol under a nitrogen atmosphere
for 1.5–2 h. Under these conditions, a number of redox
sequences occurred that gave the corresponding benzo-
thiazoles and hydroquinone with high yields and
chemoselectivities (Table 1). Substituent effects of aro-
matic terminal alkynes and aromatic iodides were also
examined. The results indicate that the reaction is relatively
insensitive to the electronic characteristics of a substituent
as well as its location.
General procedure: redox co-production
of 2-arylbenzothiazoles and hydroquinone
To a magnetically stirred solution of 0.63 g of 2-amino-
thiophenol (5 mmol) in 5 cm3 ethanol was added, in a
dropwise fashion over 5 min, 5 mmol of aromatic aldehyde
dissolved in 5 cm3 of ethanol. The mixture was stirred at
room temperature until the starting reactants were com-
pletely consumed (monitored by TLC). Then 0.54 g of 1,4-
benzoquinone (5 mmol) were added in one portion.
The color of the mixture turned dark red within 5 min,
and gradually faded to colorless as the reaction proceeded
(0.5–1 h). On completion, approximately 5 cm3 of solvent
were removed by rotary evaporation, and the residual
reaction mixture was diluted with 4 cm3 of water. The
precipitates thus formed were collected by filtration and
recystallized from 95% aqueous ethanol to afford 2-
One of the principles of green chemistry is to employ
catalysts instead of stoichiometric reagents. In the present
method, neither a stoichiometric reagent nor a catalyst is
necessary to obtain two useful products in one reaction
sequence. In other words, since no reagent is used in this
process, waste disposal becomes easier. Energy requirements
have environmental and economic impacts and should be
minimized for cleaner processing. By all appearances, our
two-in-one transformation accords with the above require-
ments in several respects, such as simplified work-up
procedure and room temperature manipulations. From the
123
Li, Guiyun
