Sulfite formation versus chlorination of benzyl alcohols with thionyl chloride

Article abstract of DOI:10.1016/j.tetlet.2014.03.116

Recently, we have reported the photolytic decay of a library of para-substituted dibenzylic sulfites in a Srinivasan-Griffin-Rayonet photochemical reactor. In an attempt to synthesize the complete library for that study we discovered that bis(p-methoxybenzyl) sulfite and bis(p-phenoxybenzyl) sulfite could not be formed and only their corresponding benzyl chlorides were synthesized. Thus, sulfite formation versus chlorination of a range of para-substituted benzyl alcohols with thionyl chloride was investigated. Sulfite formation was observed to be parabolically related to Swain and Lupton's Field ?-values while chloride formation was found to be linearly related to Swain and Lupton's Field ?-values.

Full text of DOI:10.1016/j.tetlet.2014.03.116

Tetrahedron Letters 55 (2014) 3045–3048
Contents lists available at ScienceDirect
Tetrahedron Letters
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Sulfite formation versus chlorination of benzyl alcohols
with thionyl chloride
⇑
Deana A. Rodriguez, Ronny Priefer
College of Pharmacy, Western New England University, Springfield, MA 01119, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Recently, we have reported the photolytic decay of a library of para-substituted dibenzylic sulfites in a
Srinivasan–Griffin–Rayonet photochemical reactor. In an attempt to synthesize the complete library
for that study we discovered that bis(p-methoxybenzyl) sulfite and bis(p-phenoxybenzyl) sulfite could
not be formed and only their corresponding benzyl chlorides were synthesized. Thus, sulfite formation
versus chlorination of a range of para-substituted benzyl alcohols with thionyl chloride was investigated.
Sulfite formation was observed to be parabolically related to Swain and Lupton’s Field F-values while
chloride formation was found to be linearly related to Swain and Lupton’s Field R-values.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 7 March 2014
Revised 24 March 2014
Accepted 26 March 2014
Available online 6 April 2014
Keywords:
Dibenzylic sulfite
Thionyl chloride
Swain and Lupton’s Field and Resonance
values
Chlorination
Organosulfite is a rarely used functionality. Three most com-
monly studied compounds containing this structural moiety are
dimethyl sulfite, diethyl sulfite, and propargite. Dimethyl sulfite
is commonly used as an additive in some polymers as a means to
prevent oxidation.1–3 Recently, much effort has been done on its
potential use as an electrolyte solvent for battery applications.4–6
In addition to being an antioxidant,5,6 diethyl sulfite has found
use within the grain storage industry as an antifungal agent.7
Unlike both dimethyl and diethyl sulfites, propargite is an unsym-
metrical sulfite. It is a commonly used acaricide pesticide8–10 and is
conventionally known as OmiteÒ. In addition to the killing of mites,
it is also highly toxic to plankton,11 fish,12 and amphibians.13 In the
above examples, the synthesis of the sulfite moiety is accom-
plished by the reaction of an alcohol with thionyl chloride.
Chlorination with thionyl chloride is a technique that is covered
in most undergraduate organic chemistry textbooks (Fig. 1) and is
even performed in some undergraduate teaching laboratory set-
tings. Less commonly taught, however, is that sulfite formation is
also possible with the use of the same reagent but at different reac-
tant equivalences (Fig. 1).
Recently, we synthesized a library of bis(benzyl) sulfites to study
their photolytic decay profiles.14 In the course of this investigation,
we observed that the rate of photolytic decomposition was parabol-
ically related to Swain and Lupton’s Field (F-) values, regardless of
Cl
O
S
benzyl chloride
SOCl2
OH
O
Cl
O
S
sulfonyl chloride intermediate
benzyl alcohol
O
O
bis(benzyl) sulfite
Figure 1. Chlorination and sulfite formation from the reaction of thionyl chloride and benzyl alcohol.
⇑
Corresponding author. Tel.: +1 413 796 2438; fax: +1 413 796 2266.
E-mail address: ronny.priefer@wne.edu (R. Priefer).
http://dx.doi.org/10.1016/j.tetlet.2014.03.116
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

3046
D. A. Rodriguez, R. Priefer / Tetrahedron Letters 55 (2014) 3045–3048
O
S
O
S
Cl
Cl
O
Cl
Cl-
Cl
OH
R
R
R
-HCl
R
-SO2
O
O
+
O
O
Scheme 1. Possible mechanism for the formation of benzyl chlorides opposed to bis(benzyl) sulfites.
Table 2
Table 1
Product % ratios determined by 1H NMR, using various benzyl alcohols (BA) at 5:1,
2:1, 1:1, 1:2, 1:5 ratios of BA/SOCl2
Product % ratios determined by 1H NMR, using 2:1 benzyl alcohols and thionyl
chloride at different reaction times
X-Ph-CH2OH
H
BA/SOCl2
% chloride
% sulfite
% alcohol
X-Ph-CH2OH
H
R Â n times (min)
5
60
120
180
240
300
% chloride
% sulfite
% alcohol
5:1
2:1
1:1
1:2
1:5
0
23.4
55.3
12.6
0
76.6
33.5
7.0
0
11.2
10.8
12.3
11.5
9.9
55.3
54.6
54.9
56.2
57.3
53.1
33.5
34.6
32.8
32.3
32.8
34.8
11.2
80.4
100
100
0
0
Me
tBu
Ph
5:1
2:1
1:1
1:2
1:5
0
5.9
39.8
0
0
0
94.1
27.5
18.3
0
12.1
32.7
81.7
100
100
NO2
5
60
120
180
240
300
34.0
32.2
32.8
36.2
34.8
33.4
15.4
17.1
16.2
15.0
13.8
16.0
50.6
50.7
51.0
48.8
51.4
50.6
0
5:1
2:1
1:1
1:2
1:5
6.4
10.4
60.1
0
0
0
83.2
12.9
25.6
0
27.0
74.4
100
100
Cl
5
60
120
180
240
300
7.3
5.1
6.8
8.2
8.5
7.0
67.5
66.9
68.8
68.1
64.2
67.1
25.2
28.0
24.4
23.7
27.3
25.9
0
5:1
2:1
1:1
1:2
1:5
0
14.0
29.2
0
0
0
86.0
44.5
33.9
0
26.3
66.1
100
100
0
OMe
OPh
Cl
5:1
2:1
1:1
1:2
1:5
19.1
48.6
88.1
100
100
0
0
0
0
0
80.9
51.4
11.9
0
the solvent employed. Interestingly, neither bis(p-methoxybenzyl)
sulfite nor bis(p-phenoxybenzyl) sulfite could be synthesized in
great enough quantity to further study, regardless of the reaction
temperature, solvent, time, or base used. We proposed a possible
mechanism for the formation of benzyl chlorides as opposed to
bis(benzyl) sulfites (Scheme 1),14 suggesting that electron donation
from the ether oxygen led to the displacement of SO2 prior to the
attack of another equivalent of benzyl alcohol. Interestingly, the
amounts of sulfite and chloride products formed from the other
benzyl alcohols used were dependent on the substituent at the
para-position. Herein, we report the results of our investigation of
relative sulfite formation versus chlorination upon treatment of
para-substituted benzyl alcohols with thionyl chloride.
The reported general procedure for the synthesis of sulfites
from benzyl alcohols involves reacting benzyl alcohol with thionyl
chloride and pyridine in a ratio of 2:1:2 for 5 h in dichlorometh-
ane.15 Subsequent quenching with distilled water, washing twice
with brine, drying on MgSO4, concentrating under reduced pres-
sure, and purification by column chromatography with 5:1 hex-
anes/ethyl acetate allowed for the isolation of unreacted starting
materials, benzyl chlorides, and bis(benzyl) sulfites. We began by
evaluating the reaction rate, using 1H NMR to measure product dis-
tribution for reactions with a 2:1 ratio of benzyl alcohol/thionyl
chloride at 5–300 min (Table 1). We were surprised and elated to
observe that in all cases the reaction was complete within 5 min.
We repeated this with 4-nitro- and 4-chlorobenzyl alcohols and
again observed completion of the reaction within 5 min. Impor-
tantly, the ratios of chloride to sulfite to unreacted alcohol did
not change over time, indicating the stability of the products in
solution. Thus, all subsequent reactions were run for P5 min.
In order to ascertain the effect of the para substituent on the
ratio of products, we examined the reactions of eleven different
benzyl alcohols with thionyl chloride at five different ratios, 5:1,
2:1, 1:1, 1:2, and 1:5, respectively (Table 2). [All benzyl alcohols
0
5:1
2:1
1:1
1:2
1:5
16.5
40.2
66.1
100
100
4.6
6.4
0
0
0
78.9
53.4
33.9
0
0
5:1
2:1
1:1
1:2
1:5
0
22.1
15.4
4.5
1.2
0
77.9
50.6
30.7
0
34.0
64.8
98.8
100
0
Br
5:1
2:1
1:1
1:2
1:5
0
10.7
30.1
0
0
0
89.3
34.3
9.8
0
35.6
90.2
100
100
0
CF3
CN
5:1
2:1
1:1
1:2
1:5
0
0
0
5.8
100
16.9
12.5
11.6
8.8
83.1
87.5
88.4
85.4
0
0
5:1
2:1
1:1
1:2
1:5
0
0
0
6.2
100
14.8
39.1
6.3
17.5
0
85.1
60.9
93.7
76.2
0
NO2
5:1
2:1
1:1
1:2
1:5
0
7.3
59
87.0
100
13.7
67.5
17.7
0
86.3
25.2
23.3
13.0
0
0
used were obtained from commercial sources with the exception
of 4-cyanobenzyl alcohol which was initially reduced from its

D. A. Rodriguez, R. Priefer / Tetrahedron Letters 55 (2014) 3045–3048
3047
Table 3
39% sulfite, while the same reaction with 4-tert-butylbenzyl alco-
hol afforded a product mixture consisting of 27% chloride and
60% sulfite.
Though there appeared to be no correlation of our results for
these reactions (2:1 ratio of benzyl alcohol to thionyl chloride) to
Hammett’s constant,17 we did observe that the sulfite product pre-
dominated when the para-substituent had a Swain and Lupton’s F-
value18 either on the high or low end (Table 3).
Product % ratios determined by 1H-NMR, using 2:1 benzyl alcohols and thionyl
chloride compared to Swain and Lupton’s R- and F-values
X-Ph-CH2OH
F
% sulfite
R
% chloride
tBu
H
Me
Ph
OMe
OPh
CF3
Cl
À0.02
0
60.1
55.3
39.8
29.2
0
À0.18
0
27.0
11.2
32.7
26.3
48.6
40.2
0
34
35.6
0
0.01
0.12
0.29
0.37
0.38
0.42
0.45
0.51
0.65
À0.18
À0.13
À0.56
À0.40
0.16
À0.19
À0.22
0.15
Overall, percent sulfite formation is parabolically related to
Swain and Lupton’s F-values (Fig. 2). Mechanistically, a lack of cor-
relation with Hammett’s constant for the production of sulfite can
be rationalized, since an additional atom separates the site of reac-
tion from the aromatic ring. We have observed this parabolic phe-
nomenon with Swain and Lupton’s F-value in previous studies,
particularly with the analogous dibenzylic dialkoxy disulfides
which underwent both thermolytic and photolytic decomposition
at rates that parabolically correlated to F-values,19,20 in addition
to the aforementioned bis(benzyl) sulfites photolytic decomposi-
tion study.14 It can be rationalized that a substituent with a high
F-value, such as nitro, withdraws the electron cloud toward it
and away from the sulfonyl chloride moiety, hence making it more
prone to nucleophilic attack by another benzyl alcohol (Scheme 2).
As the magnitude of the F-value decreases, this polarization differ-
ence decreases, ‘bottoming-out’ with methoxy at an F-value of
0.29. Substituents with F-values lower than methoxy, such as t-
Bu, Me, etc. that do not possess a lone pair of electrons (vide supra),
can donate electron density toward the reacting sulfur site. As a
result, the benzylic oxygen can donate a pair of electrons to the sul-
fur displacing chloride, which would thus allow for the subsequent
attack by another benzyl alcohol (Scheme 2).
While this rationale accounts for the product distribution of sul-
fite, it is not consistent with that of chloride. We observed only a
loose association of the amount of chloride product formed with
Hammett’s constants and none with Swain and Lupton’s F-values,
but we did observe a linear correlation with Swain and Lupton’s
Resonance (R-) values.18 It logically follows that the chloride prod-
uct distribution is more strongly related to a resonance effect than
an overall field effect because product formation results from
nucleophilic attack directly on the benzylic carbon. Substituents
6.4
12.5
15.4
30.1
39.1
67.5
Br
CN
NO2
0.13
7.3
Figure 2. Percent sulfite formation determined by 1H NMR, using 2:1 benzyl
alcohols and thionyl chloride versus Swain and Lupton’s F-values.
corresponding acid as previously reported.16] Significant variability
in product distribution was observed at all ratios except 1:5, in
which case only benzyl chlorides were generated. For example,
the reaction of 4-cyanobenzyl alcohol with thionyl chloride in a
ratio of 2:1 gave a product mixture consisting of 0% chloride and
Low Swain and Lupton's F-values
High Swain and Lupton's F-values
δ+
O
S
δ−
O
S
O
Cl
O
Cl
δ−
δ+
X
X
O
S
O
Cl
X
X
O
S
O
+ S
O
O
Cl
HO
HO
X
X
X
O
S
O
O
X
X
Scheme 2. Possible rationale for the formation of bis(benzyl) sulfites at high and low Swain and Lupton’s F-values.

3048
D. A. Rodriguez, R. Priefer / Tetrahedron Letters 55 (2014) 3045–3048
2:1 ratio of benzyl alcohol to thionyl chloride. Finally, we were able
to show that this reaction does not require the previously reported
5 hours, but is in fact completed after only 5 min.
Acknowledgements
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support of
this research. In addition, the authors thank the Western New
England University College of Pharmacy for their financial support.
R.P. would also like to thank Matthew Dintzner for his helpful
discussions.
References and notes
Figure 3. Percent chloride formation determined by 1H NMR, using 2:1 benzyl
alcohols and thionyl chloride versus Swain and Lupton’s R-values.
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