2
Tetrahedron
done with filter paper cut into small pieces. In an effort to
hasten the purification reaction, the aliquots were placed in an
ultrasonic cleaning bath for one hour. Ultrasonic radiation has
been shown to facilitate the interaction of solutions and solid
After sonication, the samples were washed with
1
aqueous hydrochloric acid and characterized by H NMR. The
residual amount of tosyl chloride was determined by comparing
the integrated peak area of its doublet at 7.90 ppm to the area of
the anthracene doublet of doublets at 7.99 ppm. The results of
these experiments are shown in Tables 1 and 2.
Table 1 shows that the amount of pyridine used in the tosyl
chloride removal process is important. It has been shown in
previous papers that there should be a large excess of pyridine
present during tosylation reactions. Here we show that more than
5
and preferably 10 equivalents of pyridine, compared to tosyl
chloride, are required for the complete reaction. In Table 2 an
excess of pyridine was used and the amount of cellulose was
varied. In all of the solutions, tosyl chloride was essentially
completely removed. The cellulose polymer chain, comprised of
anhydroglucose units, contains three hydroxyl moieties per repeat
unit: a single primary, which is more reactive, and two
secondary moieties that are also reactive under these conditions.
The results of Table 2 show that with a proper excess of pyridine
present, as little as 320 grams (two moles) of cellulose per mole
of tosyl chloride (191 g) will essentially completely remove the
1
3
Figure 1. Partial 500 MHz H NMR spectra (CDCl ): top) a 1:10 molar
mixture of anthracene and tosyl chloride and bottom) the mixture after
sonication with pyridine and filter paper, showing the nearly complete
removal of tosyl chloride from anthracene.
2
.2. Effect of the nature of cellulose
In a second set of experiments, different types of
1
latter from solution. Figure 1 shows stacked H NMR spectra
from before and after the reaction with pyridine and cellulose.
cellulose were tested to optimize the purification method. In this
study, only two equivalents of pyridine were used so that the
relative amounts of tosyl chloride removed from solution could
more easily be determined. Four different cellulosic materials
were tested: filter paper, semi-crystalline cellulose powder,
cotton and starch. Solutions were shaken with the cellulosic
material for eight hours, and then washed with aqueous
Table 1. Effect of pyridine concentration on reaction of TsCl
with filter paper for one hour under sonication.
a
a
Equiv. Filter Paper
Equiv. Pyridine
% Residual TsCl
1
1
1
1
3
3
3
3
2.2
4.5
9
41
1
4.3
hydrochloric acid before being characterized by H NMR. The
results of these experiments are given in Table 3. The
efficiencies were: starch > filter paper > powder >> cotton. We
initially predicted that the cellulose powder would give the best
results, but this was not the case, probably due to its semi-
crystalline nature. With nearly no change in the tosyl chloride
concentration after purification with cotton fibers this material is
not suitable for this purpose, probably due to its high level of
crystallinity. The low cost of starch and filter paper makes them
ideal for this application. However, starch tends to form a gel like
substance and stick to glassware during filtering.
0.16
0.16
13
a
Relative to TsCl. Initial concentrations of TsCl and
anthracene: 100 and 10.0 mM in CH Cl , respectively.
2
2
Table 2. Effect of amount of filter paper on residual TsCl
after one hour of sonication.
a
a
Equiv. Filter Paper
Equiv. Pyridine
% Residual TsCl
2
21
21
21
21
0.19
0.12
0.16
0.12
2.3. Application to tosylation reactions
5
.2
Finally, a series of tosylation reactions were run, and the
resulting reaction mixtures were purified using the sonication
method. Both primary and secondary alcohols were used, as well
as phenols. The tosylation employed grinding the alcohol or
phenol with 1.5 equivalents of tosyl chloride in the presence of
1
2
0
1
a
Relative to TsCl. Initial concentrations of TsCl and
anthracene: 100 and 10.0 mM in CH Cl , respectively.
potassium carbonate.
For secondary alcohols, potassium
2
2
hydroxide was also added. This method of Kazemi et al. is fast
and efficient; we found that the use of a hot mortar and pestle
caused the reaction to proceed nicely. After tosylation the
reaction mixtures were treated with pyridine and filter paper, and
then sonicated for one hour. After aqueous acidic workup, the
Table 3. Effect of cellulose type on removal of TsCl after
eight hours of shaking in CH
2
Cl
2
.
a
a
Source (2 equiv. )
Equiv. Pyridine
% Residual TsCl
1
Filter paper
Cellulose powder
Starch
2.2
2.2
2.2
2.2
63
70
59
96
compounds were characterized by H NMR to determine their
purity.
Additionally all tosylations were done in a solution of
dichloromethane with an excess of pyridine. This allowed the
simple addition of filter paper and sonication to precede the
aqueous workup steps and streamline the process. This method is
also more widely applicable than the grinding method as it does
not depend on the melting of a mixture of alcohol and tosyl
Cotton
a
Relative to TsCl. Initial concentrations of TsCl and
anthracene: 100 and 10.0 mM, respectively.
Schoonover, Daniel V.
