Comparison of cyclic and polymeric disulfides as catalysts for the regioselective chlorination of phenols

Article abstract of DOI:10.1080/17415993.2014.965170

Two cyclic and two polymeric disulfides have been synthesized and established to be useful catalysts for the chlorination of m-xylenol, o-cresol, m-cresol and phenol using freshly distilled sulfuryl chloride in the presence of aluminum or ferric chloride as a co-catalyst at room temperature. The yields of p-isomers and para/ortho ratios were higher compared to cases where no catalyst was used with most catalysts for most phenols even when a very low concentration of disulfide was used.

Full text of DOI:10.1080/17415993.2014.965170

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Comparison of cyclic and polymeric
disulfides as catalysts for the
regioselective chlorination of phenols
Keith Smitha, Ali J. Al-Zuhairia, Gamal A. El-Hitib & Mohammed B.
Alshammaric
a School of Chemistry, Cardiff University, Main Building, Park
Place, Cardiff CF10 3AT, UK
b Cornea Research Chair, Department of Optometry, College of
Applied Medical Sciences, King Saud University, PO Box 10219,
Riyadh 11433, Saudi Arabia
c Chemistry Department, College of Sciences and Humanities,
Salman bin Abdulaziz University, PO Box 83, Al-Kharij 11942,
Saudi Arabia
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Published online: 09 Oct 2014.
To cite this article: Keith Smith, Ali J. Al-Zuhairi, Gamal A. El-Hiti & Mohammed B. Alshammari
(2015) Comparison of cyclic and polymeric disulfides as catalysts for the regioselective chlorination
of phenols, Journal of Sulfur Chemistry, 36:1, 74-85, DOI: 10.1080/17415993.2014.965170
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Journal of Sulfur Chemistry, 2015
Vol. 36, No. 1, 74–85, http://dx.doi.org/10.1080/17415993.2014.965170
Comparison of cyclic and polymeric disulfides as catalysts for
the regioselective chlorination of phenols
Keith Smitha∗, Ali J. Al-Zuhairia†, Gamal A. El-Hitib and Mohammed B. Alshammaric
aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK; bCornea
Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University,
PO Box 10219, Riyadh 11433, Saudi Arabia; cChemistry Department, College of Sciences and Humanities,
Salman bin Abdulaziz University, PO Box 83, Al-Kharij 11942, Saudi Arabia
(Received 26 August 2014; accepted 9 September 2014)
Two cyclic and two polymeric disulfides have been synthesized and established to be useful catalysts for
the chlorination of m-xylenol, o-cresol, m-cresol and phenol using freshly distilled sulfuryl chloride in the
presence of aluminum or ferric chloride as a co-catalyst at room temperature. The yields of p-isomers and
para/ortho ratios were higher compared to cases where no catalyst was used with most catalysts for most
phenols even when a very low concentration of disulfide was used.
OH
OH
SO2Cl2, catalyst
AlCl3 or FeCl3
+
others
R
R
Cl
R = H, 2-Me, 3-Me, 3,5-di-Me
major
Keywords: polymeric disulfides; cyclic disulfides; phenols; chlorination; catalysts
1. Introduction
Isomerically pure chlorinated phenols are valuable materials as intermediates for industrial and
pharmaceutical chemicals.[1,2] They are also the primary active ingredients in a range of house-
hold and commercial disinfectants. In the past, crude mixtures of chlorophenols were sometimes
considered acceptable for such applications, but concerns have increased about the toxic nature
and environmental accumulation of some chlorinated phenolic compounds and their potential
by-products.[3–5] Many chlorination processes for phenols are not very selective and produce
excessive amounts of waste.[6–9] Therefore, it is important to develop chlorination catalysts
capable of minimizing undesirable waste products.
*Corresponding author. Email: smithk13@cardiff.ac.uk
†Current address: Department of Chemistry, College of Science, Babylon University, PO Box 4, Hilla, Iraq
c
ꢀ 2014 Taylor & Francis

Journal of Sulfur Chemistry 75
Chlorination of phenol with sulfuryl chloride (SO2Cl2) over partially cation-exchanged L-type
zeolite in 2,2,4-trimethylpentane was both faster and more selective than the uncatalyzed reac-
tion, giving 4-chlorophenol in 85% yield with a para/ortho (p/o) ratio of 8.[10] Reaction under
similar conditions in the presence of montmorillonite clay gave 4-chlorophenol in 76% yield with
a p/o ratio of 5.7.[10] A p/o ratio of ca. 50 can be achieved for chlorination of o-cresol by attach-
ing the o-cresol to Merrifield resin and then reacting it with sulfuryl chloride in dichloromethane
(DCM), followed by a decoupling step using trifluoroacetic acid to give the p-chloro-o-cresol in
high yield.[11] Unfortunately, the reaction involves three steps, various reagents, several differ-
ent solvents and a large quantity of Merrifield resin. Moreover, the reaction has been applied on
only a very small scale (0.33 mmol) and does not appear useful for commercial application.
Watson reported a process for the chlorination of phenols using a combination of particu-
lar divalent sulfur compounds and metal halides.[12,13] For example, chlorination of o-cresol
with sulfuryl chloride in the presence of diphenyl sulfide and aluminum chloride (AlCl3) gave
predominantly p-chloro-o-cresol (p/o ratio ca. 20). A similar process in which the sulfuryl chlo-
ride was added in portions in order to avoid solidification of the reaction mixture was also
reported.[14]
We have previously investigated the use of simple organic sulfides for the catalytic chlori-
nation reaction of phenols using sulfuryl chloride.[15,16] Unfortunately, volatile examples of
such materials are undesirable on an industrial scale because of their odors. The problem of
the volatility of such sulfides was mitigated by the use of substituted Merrifield resins and
dithiaalkanes,[17,18] but neither of these reagent types is likely to be useful commercially.
Because of the commercial importance of chlorinated phenols, methods for selective halo-
genation of phenols continue to attract attention in both the patent [19] and academic [20–24]
literature. In view of our general interests in the use of solid catalysts, which we have used
successfully to enhance the para-selectivity in aromatic electrophilic substitution reactions [25–
27] such as nitration,[28–33] halogenation,[34,35] methanesulfonylation,[36] acylation,[37,38]
and alkylation,[39,40] we decided to initiate wider studies of the use of polymeric sulfur com-
pounds for chlorination of various phenols. In this study, we report the use of two poly(alkylene
disulfides) as catalysts, with the aim to enhance para-selectivity in chlorinations of various phe-
nols. We also compare the results with those obtained using the corresponding monomeric cyclic
disulfides.
2. Results and discussion
The first task was to synthesize two cyclic disulfides: 1,2-dithiocane and 1,2-dithiolane and two
polymeric disulfides with the corresponding carbon-based spacer groups between the disulfide
units. A solution of bromine in DCM was added in a dropwise manner to a solution of 1,6-
hexanedithiol in DCM to which had been added flash chromatography grade silica gel.[41] When
a faint brown color persisted, addition of the bromine solution was stopped, and the reaction mix-
ture was filtered through a sintered glass funnel. The solid residue was washed with DCM, and
the washings were combined with the original filtrate. The solvent was removed under reduced
pressure to give 1,2-dithiocane (1; Scheme 1) in 80% yield.
The same procedure was applied for the synthesis of 1,2-dithiolane, which was obtained in
87% yield from 1,3-propanedithiol (2; Scheme 2).
Poly(trimethylene disulfide) was synthesized by the simultaneous addition of solutions of 1,3-
propanedithiol and excess iodine (I2) in chloroform (CHCl3) to a vigorously stirred solution
of triethylamine (Et3N) in CHCl3 (Scheme 3). The addition was performed over 10 h, and the
mixture was then stirred for 12 h. The mixture was washed with water and acidified with sulfuric

76 K. Smith et al.
Br2, DCM
HS
SH
hydrated silica gel
S
S
1 (80%)
Scheme 1. Synthesis of 1,2-dithiocane (1).
Br2, DCM
hydrated silica gel
SH
SH
S
S
2 (87%)
Scheme 2. Synthesis of 1,2-dithiolane (2).
I2, Et3N
CHCl3
S
HS
SH
S
x
3 (67%)
Scheme 3. Synthesis of poly(trimethylene disulfide) 3.
acid. The organic phase was washed with water, dried over magnesium sulfate (MgSO4) and
evaporated under reduced pressure to give the corresponding polymeric disulfide 3 in 67% yield.
Comparison of the integration values for the terminal SH groups with those for all other types
1
of proton signal (SCH2CH2CH2S) in the H NMR spectrum of 3 suggested that the average
number of repeating units in the synthesized polymer was ca. 6, while comparison of the inte-
gration values for methylene protons in the terminal units to those of methylene protons in the
internal units suggested that the average number of repeating units was ca. 8, but the number
average molecular weight (Mn) of the polymer, measured by gel permeation chromatography
(GPC), was found to be 1320, suggesting an average number of repeating units in the region of
12. The presence of traces of water in the sample would exaggerate the SH signal, leading to
the calculation of a smaller number of repeating units than the true figure, whereas the use of a
polystyrene standard for the GPC may exaggerate Mn for a polymer with a totally different kind
of repeating unit, but it is reasonable to assume that the polymer consisted of molecules with an
average number of repeating units in the range of 6–12 and probably close to 8.
Poly(hexamethylene disulfide) (4; 70% yield) was synthesized by a similar procedure using
1,6-hexanedithiol (Scheme 4). The integration ratio of terminal SH protons to all other protons
in the 1H NMR spectrum suggested that the average number of repeating units in the synthesized
polymer was ca. 8.5, but its Mn determined by GPC was found to be 5184, suggesting that the
average number of repeating units could be as much as four times greater. It is reasonable to
assume that the average number of repeating units in the polymer was between 8.5 and 32, but
probably nearer to the lower end of this range.
I2, Et3N
HS
S
SH
S
CHCl3
x
4 (70%)
Scheme 4. Synthesis of poly(hexamethylene disulfide) 4.

Journal of Sulfur Chemistry 77
Chlorination reactions of m-xylenol, o-cresol, m-cresol and phenol (50 mmol) were carried out
under standard conditions (addition of chlorinating agent over 2 h at room temperature, followed
by a further 2 h of stirring at room temperature) in the presence of the synthesized disulfides
1–4 (or without catalyst) using sulfuryl chloride (57.7 mmol) in the presence of a Lewis acid as
a co-catalyst. The chlorination of m-xylenol (MX) in the presence of FeCl3 as the Lewis acid
(Scheme 5) was studied first.
OH
OH
OH
OH
Cl
Cl
SO2Cl2, catalyst
FeCl3
+
+
Cl
Cl
MX
PCMX
OCMX
DCMX
Scheme 5. Chlorination of m-xylenol.
The chlorination of m-xylenol (50 mmol) using SO2Cl2 (57.7 mmol) in the presence of a cyclic
disulfide (30 mg) and ferric chloride (FeCl3; 25 mg) in DCM (25 ml) gave the results shown in
Table 1.
As can be seen from Table 1, both cyclic disulfides brought about greater selectivity for the
formation of para-chloro-meta-xylenol (PCMX) than in the absence of any disulfide, but 1,2-
dithiolane (2) resulted in greater selectivity than 1,2-dithiocane (1), giving PCMX in 91.8%
yield with a p/o ratio of 19.1.
Poly(alkylene disulfides) (3; n = 3 or 4; n = 6) were next tested as potential catalysts for the
chlorination of m-xylenol under the same conditions (Table 2). Both polymers 3 and 4 acted
as selective catalysts, but poly(trimethylene disulfide) 3 resulted in greater para-selectivity than
poly(hexamethylene disulfide) 4. However, a significant decrease in the amount of the hexam-
ethylene disulfide polymer 4 (n = 6) from 30 to only 1 mg had almost no deleterious effect on
the selectivity, while a similar decrease in the amount of the poly(trimethylene disulfide) 3 from
30 to only 1 mg had a deleterious effect on the selectivity. Interestingly, each polymeric disul-
fide resulted in greater selectivity than its corresponding monomeric cyclic disulfide, and within
each series (monomeric and polymeric) the catalyst having a trimethylene spacer demonstrated
greater selectivity than that with a hexamethylene spacer.
Similar reactions to those reported in Tables 1 and 2 were conducted with AlCl3 as the Lewis
acid rather than FeCl3. The results were broadly comparable, but the reactions conducted in the
Table 1. Chlorination of m-xylenol in the presence of cyclic disulfides 1 and 2 and FeCl3.a
Yield (%)b
Catalyst
MX
OCMX
PCMX
DCMX
p/o ratio
Mass balance (%)c
—
1
3.0 (4.5)
0.0
10.0 (11.3)
7.6
84.6 (82.0)
89.0
0.2 (1.0)
3.3
8.4 (7.2)
11.7
97.8 (98.8)
99.9
2
0.7
4.8
91.8
2.0
19.1
99.3
aSO2Cl2 (4.66 ml and 57.7 mmol) was slowly added to a mixture of m-xylenol (6.11 g and 50.0 mmol), FeCl3 (25 mg), and the catalyst
(30 mg) in DCM (25 ml) at room temperature over 2 h, and then the mixture was allowed to stir for another 2 h before it was worked up.
bYield percentage was calculated using quantitative GC. Figures in parentheses are for the reaction carried out in the absence of FeCl3.
cMass balances are calculated by adding together the yields of identified compounds; any deficiency from 100% represents unidentified
components or experimental measurement errors.

78 K. Smith et al.
Table 2. Chlorination of m-xylenol in the presence of poly(alkylene disulfides) and FeCl3.a
Yield (%)b
(CH2)n
S
S
x
3 or 4 (mg)
MX
OCMX
PCMX
DCMX
p/o ratio
Mass balance (%)c
—
3.0 (4.5) 10.0 (11.3) 84.6 (82.0) 0.2 (1.0)
8.4 (7.2)
23.8
20.5
15.3
14.9
97.8 (98.8)
98.9
99.0
99.5
99.9
100.1
3 (30)
3 (10)
3 (1)
4 (30)
4 (1)
0.0
0.0
0.5
1.5
2.3
3.9
4.5
6.0
6.0
6.4
93.0
92.5
92.0
89.9
89.0
2.0
2.0
1.0
2.5
3.4
13.9
a,b,cSee Footnotes a, b and c in Table 1.
presence of AlCl3 were slightly more selective for the formation of the p-isomer. Therefore,
reactions with other phenols were conducted in the presence of AlCl3 rather than FeCl3.
Our attention was next turned to chlorination of o-cresol (OC) using the disulfide catalysts
(Scheme 6). In this case, it was not necessary to use a solvent for the reactions since the substrate
could be melted and would then remain liquid at 20°C in the presence of other materials. First we
attempted the use of various quantities of 1,2-dithiocane (1; 1–100 mg for 50 mmol of o-cresol)
as a catalyst. The results are shown in Table 3, along with the baseline results for the chlorination
of o-cresol in the absence of any disulfide catalyst.
OH
OH
OH
Cl
SO2Cl2, catalyst
AlCl3
+
Cl
OC
PCOC
OCOC
Scheme 6. Chlorination of o-cresol.
Table 3 shows that 1,2-dithiocane (1) acts as a selective catalyst for the chlorination of o-cresol,
giving yields of p-isomer in the range of 93–95%. Also, a significant decrease in the amount of
Table 3. Chlorination of o-cresol in the presence of 1,2-dithiocane (1) and AlCl3.a
Yield (%)b
Mass balance (%)c
S
S
1 (mg)
OC
OCOC
PCOC
p/o ratio
—
14.0 (15.0)
9.0 (9.3)
4.6
5.0
5.5
6.0
76.0 (75.6)
95.0
8.4 (8.1)
20.6
19.0
17.0
16.0
99.0 (99.8)
100.0
100.0
99.5
100
50
10
1
0.4
0.0
1.0
0.3
0.0
1.4
95.0
93.0
93.6
92.1
99.9
99.1
99.4
1d
7.0
6.5
13.0
14.0
0.5d
91.5
aSO2Cl2 (4.66 ml and 57.7 mmol) was slowly added to a mixture of o-cresol (5.41 g and 50.0 mmol), AlCl3 (0.25 g) and the catalyst at
room temperature over 2 h, and then the mixture was allowed to stir for another 2 h before it was worked up.
bYield percentage was calculated using quantitative GC. Figures in parentheses are for the reaction carried out in the absence of AlCl3.
cSee Footnote c in Table 1.
dThe reaction was scaled up four-fold to 200 mmol of o-cresol to enable the use of smaller quantities of catalyst with relatively high
accuracy. The actual amounts of catalyst used were therefore four times the figures recorded in the table.

Journal of Sulfur Chemistry 79
catalyst (from 100 to 1 mg) had only a small effect on the selectivity. For example, the selectivity
towards the p-isomer dropped from 17 to 16 on reducing the quantity of catalyst from 10 to
only 1 mg for 50 mmol of o-cresol. Even a further decrease in the amount of catalyst (from 4
to 2 mg for 200 mmol of o-cresol) had only a slight effect on the selectivity and the yield of
para-chloro-ortho-cresol (PCOC).
Chlorination of o-cresol was also carried out in the presence of 1,2-dithiolane (2; 1–100 mg for
50 mmol of o-cresol) as a catalyst under the same conditions. The results are shown in Table 4.
Table 4 shows that 1,2-dithiolane (2) was also a selective catalyst for the chlorination of o-
cresol. Yields of around 93% for the desired PCOC were obtainable. Also, the p/o ratio was
nearly constant (16.6–15.0) on changing the quantity of catalyst from 100 to 1 mg. Clearly, both
1,2-dithiocane (1) and 1,2-dithiolane (2) behaved in a similar manner in terms of selectivity and
yield of PCOC, except that 1 induced greater selectivity than 2 at higher amounts of catalyst.
Also, poly(trimethylene disulfide) 3 and poly(hexamethylene disulfide) 4 were tested as cat-
alysts for the chlorination of o-cresol under the standard conditions established previously with
cyclic disulfides, and the results obtained are shown in Table 5.
Table 5 shows that both poly(trimethylene disulfide) 3 and poly(hexamethylene disulfide) 4
gave high para-selectivity, with yields of PCOC in the range of 90–92.5% with just 1 mg of cat-
alyst for 50 mmol of o-cresol. Furthermore, dramatically decreasing the amount of catalyst from
100 to 1 mg had only a modest effect on the selectivity with either of the polymeric disulfides.
Interestingly, while the cyclic compound with a hexamethylene spacer (i.e. 1) was somewhat
more effective than that with a trimethylene spacer (2), the situation was reversed for the poly-
meric materials, with poly(trimethylene disulfide) showing slightly greater effectiveness than
poly(hexamethylene disulfide).
Cyclic and polymeric disulfides 1 and 2 were next tested as catalysts in chlorination of m-
cresol (MC) under the standard conditions. The quantities of catalysts were varied from 100 to
Table 4. Chlorination of o-cresol in the presence of 1,2-dithiolane (2).a
Yield (%)b
Mass balance (%)c
S
S
2 (mg)
OC
OCOC
PCOC
p/o ratio
—
100
50
1
14.0 (15.0)
9.0 (9.3)
5.6
6.0
76.0 (75.6)
93.0
8.4 (8.1)
16.6
15.5
99.0 (99.8)
99.6
1.0
0.6
0.2
93.2
93.0
99.8
99.4
6.2
15.0
a,b,cSee Footnotes a, b and c in Table 3.
Table 5. Chlorination of o-cresol using different polyalkylene disulfides 3 and 4 and AlCl3.a
Yield (%)b
(CH2)n
S
S
x
3 or 4 (mg)
OC
OCOC
PCOC
p/o ratio
Mass balance (%)c
—
14.0 (15.0) 9.0 (9.3) 76.0 (75.6)
8.4 (8.1)
18.7
17.2
17.0
14.4
99.0 (99.8)
99.6
3 (100)
3 (50)
3 (10)
3 (1)
4 (100)
4 (1)
0.9
0.8
1.0
0.5
1.0
0.5
5.0
5.4
5.5
6.4
6.5
9.0
93.7
93.4
93.0
92.5
93.0
90.0
99.6
99.5
99.4
100.5
99.5
14.0
10.0
a,bSee Footnotes a and b in Table 3.
cSee Footnote c in Table 1.

80 K. Smith et al.
only 1 mg for 50 mmol of m-cresol in the presence of AlCl3 as a co-catalyst in a solvent-free
system (Scheme 7). The results are shown in Tables 6 and 7, along with the baseline results for
the chlorination of m-cresol in the absence of any catalyst.
OH
OH
OH
OH
Cl
Cl
SO2Cl2, catalyst
AlCl3
+
+
Cl
MC
PCMC
OCMC
Scheme 7. Chlorination of m-cresol.
From Table 6 it is noticeable that both 1,2-dithiocane (1) and 1,2-dithiolane (2) act as selective
catalysts for the chlorination of m-cresol compared to the situation where no catalyst is used.
Both catalysts show comparable results, and it is noteworthy that a considerable decrease in the
quantity of either catalyst had only a modest effect on the selectivity.
Table 6. Chlorination of m-cresol in the presence of 1,2-dithiocane (1) or 1,2-dithiolane (2) and AlCl3.a
Yield (%)b,c
Cyclic disulfide 1 or 2 (mg)
MC
OCMC
PCMC
p/o ratio
Mass balance (%)d
(—)
2.5 (3.2)
0.5
1.0
0.5
1.0
9.5 (10.0)
6.0
87.2 (86.0)
93.0
9.1 (8.6)
15.5
13.0
13.1
10.5
99.2 (99.2)
99.5
1 (100)
1 (50)
1 (10)
1 (1)
7.0
7.0
8.5
91.5
92.0
90.0
99.5
99.5
99.5
2 (50)
2 (1)
1.3
0.2
7.0
8.1
91.5
91.6
13.0
11.3
99.8
99.9
aSO2Cl2 (4.66 ml and 57.7 mmol) was slowly added to a mixture of m-cresol (5.41 g and 50.0 mmol), AlCl3 (0.25 g) and the catalyst at
room temperature over 2 h, and then the mixture was allowed to stir for another 2 h before it was worked up.
bSee Footnote b in Table 3.
cThe two ortho-chlorinated products have been grouped under the auspices of OCMC because the two isomers were not separated by the
GC system used.
dSee Footnote c in Table 1.
Table 7. Chlorination of m-cresol in the presence of polyalkylene disulfide 3 or 4 and AlCl3.a
Yield (%)b,c
(CH2)n
S
S
x
3 or 4 (mg)
MC
OCMC
PCMC
p/o ratio
Mass balance (%)d
—
3 (100)
3 (1)
2.5 (3.2)
0.8
0.0
9.5 (10)
9.0
9.7
87.2 (86.0)
91.0
9.1 (8.6)
10.1
9.2
99.2 (99.2)
100.8
90.0
99.7
4 (100)
4 (1)
0.7
0.5
8.9
9.0
90.5
90.0
10.1
10.0
100.1
99.5
a,cSee Footnotes a and c in Table 6.
bSee Footnote b in Table 3.
dSee footnote c in Table 1.

Journal of Sulfur Chemistry 81
From Table 7 it is clear that neither poly(hexamethylene disulfide) 3 nor poly(trimethylene
disulfide) 4 had much effect on selectivity over the uncatalyzed reaction. The yield of para-
chloro-meta-cresol (PCMC) was in the range of 90–91% with both catalysts, irrespective of the
quantity of catalyst.
Finally, we attempted the use of the cyclic and polymeric disulfides as potential selective
catalysts in the chlorination of phenol (P, Scheme 8) in a solvent-free system (following initial
melting of the phenol, which then remained liquid in the presence of the other materials used in
the reaction) under otherwise standard conditions. The results are recorded in Table 8.
OH
OH
OH
OH
Cl
Cl
SO2Cl2, catalyst
AlCl3
+
+
Cl
Cl
P
Scheme 8. Chlorination of phenol.
PCP
OCP
PDCP
As Table 8 shows, chlorination of phenol with any disulfide present was more selective than
when no catalyst was used, and with any specific disulfide the result was virtually identical with
either 50 or 1 mg of the material. The materials with a hexamethylene spacer encouraged greater
para-selectivity than their counterparts with a trimethylene spacer, and the cyclic monomers
encouraged greater para-selectivity than their polymeric counterparts. Consequently, 1,2-
dithiocane (1) was the most selective catalyst for chlorination of phenol, giving 4-chlorophenol
(PCP) in 91% yield with a p/o ratio of 13 even when only 1 mg of catalyst was used.
It is notable that an increase in para-selectivity compared with cases where no catalyst
was used has been achieved with most catalysts for most phenols. This can be understood
in terms of the mechanistic rationalization put forward by Watson in his original report of
catalysis by diphenyl sulfide, wherein he proposed that the actual electrophilic agent was
bulky chlorodiphenylsulfonium tetrachloroaluminate, which therefore favored attack at the less-
hindered para-position of o-cresol.[12,13] However, the more subtle effects observed in the
present study are more difficult to rationalize on this simple basis alone.
Table 8. Chlorination of phenol in the presence of cyclic and polymeric disulfides and AlCl3.a
Yield (%)b
Catalyst (mg)
P
OCP
PCP
PDCP
p/o ratio
Mass balance (%)c
—
6.0 (6.5)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
19.0 (20.2)
7.4
73.0 (71.0)
91.2
2.0 (1.5)
1.1
2.3
3.8
4.5
2.3
3.5
2.4
2.2
3.8 (3.5)
12.3
13.0
9.6
9.3
8.7
8.6
10.2
10.0
100 (99.2)
99.7
100.3
99.8
99.7
99.8
100.0
99.5
100.0
1 (50)
1 (1)
2 (50)
2 (1)
3 (50)
3 (1)
4 (50)
4 (1)
7.0
9.0
9.2
10.0
10.0
8.6
91.0
87.0
86.0
87.5
86.5
88.5
89.0
8.8
aSO2Cl2 (4.66 ml and 57.7 mmol) was slowly added to a mixture of phenol (4.71 g and 50.0 mmol), AlCl3 (50 mg) and the catalyst (50
or 1 mg) at room temperature over 2 h, and then the mixture was allowed to stir for another 4 h before it was worked up.
bSee Footnote b in Table 3.
cSee Footnote c in Table 1.

82 K. Smith et al.
For example, the ring size of cyclic disulfides played an important role in terms of selectiv-
ity in the chlorination of some phenols. In particular, 1,2-dithiolane gave better para-selectivity
compared to 1,2-dithiocane for the chlorination of m-xylenol and phenol. On the other hand,
1,2-dithiocane was somewhat better than 1,2-dithiolane for para-selectivity in the chlorination of
o-cresol when a large quantity of catalyst was used. The ring size was found to have almost no
effect in the chlorination of m-cresol. Also, poly(trimethylene disulfide) showed a higher selec-
tivity than poly(hexamethylene disulfide) for the chlorination of m-xylenol and o-cresol, whereas
poly(hexamethylene disulfide) was better for selectivity than poly(trimethylene disulfide) in the
chlorination of phenol, while both polymeric disulfides showed similar selectivity for the chlo-
rination of m-cresol. At this point it is not clear what causes these subtle effects, but we are
currently undertaking studies with other catalysts, which may help to clarify the issue.
3. Conclusions
Two cyclic and two polymeric disulfides have been established as useful catalysts for the
chlorination of various phenols using sulfuryl chloride in the presence of a Lewis acid.
4. Experimental section
4.1. General
Chemicals and phenol derivatives were purchased from Aldrich and Lancaster chemicals, and
mostly used without further purification. Sulfuryl chloride was distilled at ambient pressure under
an inert atmosphere. All GC analyses were carried out on a Shimadzu GC-2014 Gas Chromato-
graph using a capillary ZB Carbowax column (30 m, 0.32 mm ID). The GC conditions used
for analysis were 40°C for 3 min, ramped to 220°C at 10°C/min and held for 8 min. The injec-
tion temperature was 300°C and the detection temperature 250°C. Tetradecane was added as an
internal standard to allow quantification. All of the expected products from chlorination of phe-
nols were purchased from Aldrich Chemical Company and used to determine retention times
1
and response factors for each product. H and 13C NMR spectra were recorded on a Bruker
AV500 spectrometer operating at 500 MHz for 1H and 125 MHz for 13C measurements. Chem-
ical shifts δ are reported in parts per million (ppm) relative to TMS, and coupling constants J
are in Hz and have been rounded to the nearest whole number. 13C multiplicities were revealed
by DEPT signals. Assignments of signals are based on integration values, coupling patterns and
expected chemical shift values and have not been rigorously confirmed. Low-resolution mass
spectrometric data were recorded on a Fisons VG Platform II quadrupole instrument, and high-
resolution mass spectrometric data were recorded on a Waters Q-TOF micromass spectrometer.
GPC was carried out using a GPC MAX variable loop equipped with two KF-805 L SHODEX
columns in THF, with a RI(VE3580) detector using a GPC MAX pump operating at a flow rate
of 1 ml/min. Calibration was achieved using a series of Viscotek polystyrene standards up to
Mw = 9.4 × 105.
4.2. Typical experimental procedure for the preparation of cyclic disulfides 1 and 2
Water (2.5 ml) was added dropwise via a syringe to stirred chromatography grade silica gel
(5.0 g) in a 100 ml round-bottomed flask fitted with a septum. Stirring was continued until a
free-flowing powder was obtained, which took a few minutes. DCM (25 ml) was added to the

Journal of Sulfur Chemistry 83
flask followed by a solution of alkanedithiol (4.02 mmol) in DCM (5 ml). A solution of bromine
in DCM (1.16 M, 3.5 ml and 4.06 mmol) was added dropwise via a syringe to the reaction mix-
ture. The characteristic brown color of the bromine disappeared as soon as the bromine solution
came into contact with the reaction mixture in the flask. However, when a faint brown color per-
sisted, indicating that the reaction was complete, the addition of bromine solution was stopped,
and the reaction mixture was filtered through a sintered glass funnel. The solid was washed with
DCM (60 ml) and filtered, and residual solvent was removed to give the product.
4.2.1. 1,2-Dithiocane (1)
Yield 0.47 g (3.2 mmol; 80%) from 1,6-hexanedithiol (0.60 g; 4.0 mmol); Mp 45–47°C (Lit. [42]
bp. 60–64°C at 1 torr); 1H NMR (CDCl3) δ (ppm): 1.30 (m, 4 H, CH2CH2CH2SS), 1.65 (m, 4
H, CH2CH2CH2SS), 2.65 (app. t, J = 7 Hz, 4 H, CH2SS); 13C NMR (CDCl3) δ (ppm): 27.5 (t,
CH2CH2CH2SS), 29.1 (t, CH2CH2SS), 38.9 (t, CH2SS); EI-MS (m/z, %): 148 (M+, 37), 116
([M – S]+, 25), 101 (20), 87 (100), 84 ([M – 2 S]+, 25); HRMS (EI): calcd for C6H12S2 (M+):
148.0380; found: 148.0376.
4.2.2. 1,2-Dithiolane (2)
1
Yield 0.36 g (3.4 mmol; 87%) from 1,3-propanedithiol (0.43 g; 4.0 mmol); oily gel; H NMR
(CDCl3) δ (ppm): 1.80 (m, 2 H, CH2CH2SS), 3.35 (app. t, J = 7 Hz, 4 H, CH2SS); 13C NMR
(CDCl3) δ (ppm): 28.5 (t, CH2CH2SS), 37.9 (t, CH2SS); EI-MS (m/z, %): 106 (M+, 100), 78
(37), 73 ([M – SH]+, 10), 59 (10), 64 (8); HRMS (EI): calcd for C3H6S2 (M+): 105.9950; found:
105.9947.
4.3. Typical experimental procedure for the preparation of polyalkylene disulfides 3 and 4
A solution of alkanedithiol (10.0 mmol) in chloroform (10 ml) and a solution of iodine (2.66 g,
10.5 mmol) in chloroform (45 ml) were added simultaneously to a vigorously stirred solution
of triethylamine (2.22 g, 22.0 mmol) in chloroform (25 ml) over 10 h, and the mixture was then
stirred for 12 h. The mixture was quenched by the addition of water (40 ml) followed by sulfuric
acid (0.1 M, 20 ml). The organic layer was separated and washed with water (20 ml). The organic
phase was dried over MgSO4, and the solvent was removed under reduced pressure to give the
product.
4.3.1. Poly(trimethylene disulfide) 3
Yield 0.71 g (6.7 mmol; 67%) from 1,3-propanedithol (1.08 g; 10 mmol); Mp 90–94°C; 1H NMR
(CDCl3) δ (ppm): 1.20 (s, 2 H, terminal SH), 2.0–2.4 (m, 11.6 H, CH2CH2S), 2.85 (t, J = 7
Hz, 2.6 H, terminal CH2SH), 2.95 (t, J = 7 Hz, 2.6 H, terminal CH2CH2CH2SH), 3.15 (app.
t, J = 7 Hz, 16 H, CH2SS); 13C NMR (CDCl3) δ (ppm): many signals grouped into two sets
centered around 33.5 (t, CH2CH2S), 38.9 (t, CH2S). Mn (GPC): 1320.
4.3.2. Poly(hexamethylene disulfide) 4
1
Yield 1.03 g (7.0 mmol; 70%) from 1,6-hexanedithiol (1.50 g; 10 mmol); Mp 110–115°C; H
NMR (CDCl3) δ (ppm): 1.30–1.45 (m, 34 H, CH2CH2CH2S), 1.51 (s, 2.0 H, terminal SH), 1.55–
1.75 (m, 34 H, CH2CH2CH2S), 2.55–2.75 (m, 34 H, CH2S); 13C NMR (CDCl3) δ (ppm): many

84 K. Smith et al.
signals grouped into three sets centered around 28.4 (t, CH2CH2CH2S), 29.5 (t, CH2CH2S), 39.6
(t, CH2S). Mn (GPC): 5184.
4.4. Typical experimental procedure for the chlorination of m-xylenol
m-Xylenol (6.11 g, 50.0 mmol), FeCl3 (25 mg), DCM (25 ml) and the catalyst (30 mg) were
added to a dried 50 ml round-bottomed flask. Freshly distilled sulfuryl chloride (4.66 ml, 57.7
mmol) was added slowly over 2 h via a pressure-equalizing dropping funnel. The reaction was
stirred at room temperature for a further 2 h. The mixture was quenched with water (20 ml),
and the organic components were extracted with diethyl ether (3 × 30 ml). The ether layers
were removed, combined and dried over MgSO4. The drying agent was filtered, and the solvent
was removed under reduced pressure. The crude product was weighed and then analyzed by
quantitative GC.
4.5. Typical experimental procedure for the chlorination of o-cresol and m-cresol
o-Cresol (melted) or m-cresol (5.41 g, 50.0 mmol), AlCl3 (0.25 g) and the catalyst (100 mg)
were added to a dried 50 ml round-bottomed flask. Sulfuryl chloride (4.66 ml, 57.7 mmol) was
then added slowly over 2 h via a pressure-equalizing dropping funnel. The reaction mixture was
stirred for 2 h before being quenched with water (20 ml). The reaction mixture was worked up,
and the crude products were weighed until constant mass and then analyzed by quantitative GC.
4.6. Typical experimental procedure for the chlorination of phenol
Phenol (melted; 4.71 g, 50.0 mmol), AlCl3 (0.25 g) and a catalyst (50 mg) were added to a dried
50 ml round-bottomed flask. Sulfuryl chloride (4.66 ml, 57.7 mmol) was added slowly over 2
h via a pressure-equalizing dropping funnel. The reaction mixture was stirred for 4 h and then
quenched by the addition of water (20 ml). The reaction mixture was worked up, and the crude
products were weighed until constant mass and then analyzed by quantitative GC.
Acknowledgements
This project was supported by the Deanship of Scientific Research at Salman bin Abdulaziz University under the research
project 2013/01/134 and the Iraqi Government.
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