para-Selective chlorination of cresols and m-xylenol using sulfuryl chloride in the presence of poly(alkylene sulfide)s

Article abstract of DOI:10.1080/17415993.2020.1740226

Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chloride in the presence of a range of poly(alkylene sulfide)s and a Lewis acid (aluminum or ferric chloride) has been studied. The sulfur containing catalysts used led to the production of para-chlorophenols in high yields and higher para/ortho ratios than for reactions in the absence of such poly(alkylene sulfide)s. The effectiveness of the polymers was found to be dependent on the length of the spacer groups between the sulfur atoms. For example, polymers with shorter spacers provided high yields of 4-chloro-o-cresol (ca. 97%), while polymers with at least one longer spacer provided high yields of both 4-chloro-m-cresol (up to 94.6%) and 4-chloro-m-xylenol (up to 97.6%).

Full text of DOI:10.1080/17415993.2020.1740226

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
para-Selective chlorination of cresols and m-
xylenol using sulfuryl chloride in the presence of
poly(alkylene sulfide)s
Keith Smith, Amany S. Hegazy & Gamal A. El-Hiti
To cite this article: Keith Smith, Amany S. Hegazy & Gamal A. El-Hiti (2020): para-Selective
chlorination of cresols and m-xylenol using sulfuryl chloride in the presence of poly(alkylene
sulfide)s, Journal of Sulfur Chemistry
To link to this article: https://doi.org/10.1080/17415993.2020.1740226
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2020.1740226
para-Selective chlorination of cresols and m-xylenol using
sulfuryl chloride in the presence of poly(alkylene sulfide)s
c
Keith Smith a, Amany S. Hegazya,b and Gamal A. El-Hiti
aSchool of Chemistry, Cardiff University, Cardiff, UK; bDepartment of Chemistry, University of Wales, Swansea,
UK; cCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud
University, Riyadh, Saudi Arabia
ABSTRACT
ARTICLE HISTORY
Received 24 February 2020
Accepted 4 March 2020
Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chlo-
ride in the presence of a range of poly(alkylene sulfide)s and a Lewis
acid (aluminum or ferric chloride) has been studied. The sulfur con-
taining catalysts used led to the production of para-chlorophenols
in high yields and higher para/ortho ratios than for reactions in the
absence of such poly(alkylene sulfide)s. The effectiveness of the poly-
mers was found to be dependent on the length of the spacer groups
between the sulfur atoms. For example, polymers with shorter spac-
ers provided high yields of 4-chloro-o-cresol (ca. 97%), while poly-
mers with at least one longer spacer provided high yields of both 4-
chloro-m-cresol (up to 94.6%) and 4-chloro-m-xylenol (up to 97.6%).
KEYWORDS
Poly(alkylene sulfide)s;
o-cresol; m-cresol; m-xylenol;
para-selective chlorination;
sulfuryl chloride; Lewis acid
1. Introduction
Chlorinated phenols belong to an important class of organic compounds with wide utility.
They are produced on industrial scale and are involved in the production of pharmaceu-
ticals, dyes, herbicides, pesticides, and antiseptics [1]. For example, 4-chloro-m-xylenol
(4-CMX) is used as a disinfectant in households and hospitals [2–4]. It is effective against
Gram-positive bacteria through inhibition of their cell wall biosynthesis [5]. Also, 4-
chloro-o-cresol (4-COC) is used in the production of fungicides [6]. Chlorination of
phenols has traditionally been conducted in the liquid phase using molecular chlorine
as the chlorinating reagent and in the presence of a Lewis acid, but such processes lead
to mixtures of isomers with low selectivity towards the more desirable para-isomers [7].
CONTACT Keith Smith
Place, Cardiff CF10 3AT, UK; Gamal A. El-Hiti
smithk13@cardiff.ac.uk
School of Chemistry, Cardiff University, Main Building, Park
Cornea Research Chair, Department of
gelhiti@ksu.edu.sa
Optometry, College of Applied Medical Sciences, King Saud University, PO Box 10219, Riyadh 11433, Saudi Arabia
© 2020 Informa UK Limited, trading as Taylor & Francis Group

2
K. SMITH ET AL.
For industrial applications nowadays, chlorophenols need to be produced more selectively
in high yields without generation of the large quantities of waste associated with the tra-
ditional chlorination processes [8–10]. Recently, various chlorinating systems for phenols
have been developed, but most were selective towards the synthesis of ortho-chlorophenols
[11–15].
Zeolites and other acidic solids have been used as catalysts in para-selective halogena-
tion of organic compounds [16–21], but only a little success has been achieved in this
way with phenols [10]. Chlorination of o-cresol (OC) using sulfuryl chloride (SO2Cl2)
in the presence of aluminum-pillared montmorillonite in 2,2,4-trimethylpentane led to
a para/ortho ratio of only 6.1 with a conversion of 98% [10]. The use of the acidic solid
catalyst eliminated the need for a Lewis acid, but the need for a long reaction time and
an excessive amount of solvent and the modest yield of para-isomer render the process
unattractive for commercial application.
Several other processes have been developed for the para-selective chlorination of
phenols. For example, chlorination of OC bound to Merrifield resin using SO2Cl2 in
dichloromethane (DCM) at 25°C gave a para/ortho ratio of 50 according to analysis of
the 1H-NMR spectrum of the mixture of chloro-ortho-cresols formed [22]. However, the
process is not practical since it involves coupling of OC to the resin, and then decoupling
steps to free the chlorinated products after chlorination. In addition, the reaction time was
long (more than 48 h), various solvents (dimethylformamide and DCM) and reagents (cae-
sium carbonate, sodium iodide and trifluoroacetic acid) were used in the process, and the
reaction was conducted on only a very small scale (0.33 mmol).
Selective chlorinating systems involving use of sulfur-containing catalysts and SO2Cl2
have been developed [23–27]. For example, the SO2Cl2/diphenyl sulfide (Ph2S)/aluminum
chloride (AlCl3) system was efficient in chlorination of OC and m-cresol (MC) to
give the para-isomers in 94% yield (para/ortho ratio = 19) and 83% yield (para/ortho
ratio = 7.5), respectively [23,24]. Similarly, chlorination of m-xylenol (MX) using the
SO2Cl2/Ph2S/ferric chloride (FeCl3) system gave the corresponding 4-CMX and 2-chloro-
m-xylenol (2-CMX) in 89.9 and 2.4% yields, respectively [25]. Chlorination of MC using
the SO2Cl2/dibutyl sulfide (Bu2S)/AlCl3 system gave 4-chloro-m-cresol (4-CMC) in 89.9%
yield with a para/ortho ratio of 17.3 [26], but an even better yield of 4-CMC (95.5%) with
a para/ortho ratio of 20.7 was achieved when 5,18-dithiadocosane was used as the catalyst
instead of Bu2S [27].
Cyclic and polymeric disulfides have also been used as selective catalysts for the pro-
duction para-chlorophenols [28]. For example, chlorination of OC using the SO2Cl2/1,2-
dithiocane/AlCl3 system led to the production of 4-COC in a yield of up to 95% with a
para/ortho ratio of 20.6, while 1,2-dithiolane or polyalkylene disulfides under similar reac-
tion conditions led to formation of 4-COC in yields of up to 93.2% (para/ortho = 16.6) or
93.7% (para/ortho = 18.7), respectively [28]. With MC under similar reaction conditions
4-CMC was produced in a yield up to 93% with a para/ortho ratio of 15.5 [28]. Chlorination
of MX using cyclic or polymeric disulfides in the presence of FeCl3 in DCM as sol-
vent gave 4-CMX in a yield up to 91.8% (para/ortho = 19.1) or 93% (para/ortho = 23.8),
respectively [28].
Methylthioalkanes containing a second functional group (OH, OMe, or SMe) have also
been used as selective catalysts for the chlorination of phenols using SO2Cl2 and a Lewis
acid [29]. The catalysts with smaller numbers of spacer methylene groups (2 or 3) between

JOURNAL OF SULFUR CHEMISTRY
3
the SMe group and the second functionality provided betterpara-selectivity in chlorination
of MC and MX, but those with longer spacers (6 or 9 methylene units) provided higher
para-selectivity in chlorination of OC [29].
Recently, we have synthesized a range of poly(alkylene sulfide)s [30,31] and shown that
they act as para-selective catalysts for the production of 2,4-dichlorophenol in up to 97.1%
yield from either chlorination of 2-chloropheneol or double chlorination of phenol [31].
para-Chlorinated products of OC, MC, and MX are commercially important and it was
therefore, of interest to test the poly(alkylene sulfide) catalysts in chlorination of these
phenols under similar reaction conditions. Now, we report an efficient procedure for the
production of the corresponding 4-COC, 4-CMC, and 4-CMX in high yield and selectivity.
2. Results and discussion
Poly(alkylene sulfide)s 1–26 (Figure 1) were available from previous work [31]. They varied
in the method of synthesis, involving the use of either organolithium reagents (polymers
1–19) or sodium sulfide (polymers 20–29), the length of the spacer groups between the sul-
fur atoms (n, m = 2–12), the nature of the terminal groups (nominally Br or Bu, depending
on the method of synthesis), and their symmetry (whether or not n = m).
Chlorination of melted OC (100 mmol) using freshly distilled SO2Cl2 (110 mmol) in
the presence of poly(alkylene sulfide)s 1–26 (0.2 g) and AlCl3 (0.2 g) was attempted at 20°C
(Scheme 1). For comparison, the reaction was performed in the absence of any catalyst to
provide the baseline result. The yields of 2-chloro-o-cresol (2-COC) and 4-COC are shown
in Table 1.
Table 1 shows that all polymers benefitted both the yield of 4-COC and the para/ortho
ratio, and the differences in performance were not huge. In general, polymers with at least
one shorter chain (three or four methylene groups between the sulfur atoms) seemed
to produce somewhat better para/ortho ratios than those with only longer chains, and
those that were produced by the organolithium method (i.e. polymers 1–19) in general
gave somewhat better results than those produced by the sodium sulfide method (i.e.
polymers 20–26). Similar observations have been made in chlorination of phenol and
2-chlorophenol in the presence of these catalysts [31].
Figure 1. Poly(alkylene sulfide)s 1–26.
Scheme 1. Chlorination of o-cresol using sulfuryl chloride and poly(alkylene sulfide)s 1–26.

4
K. SMITH ET AL.
Table 1. Chlorination of o-cresol using sulfuryl chloride and poly(alkylene sulfide)s 1–26 as catalysts in
the presence of AlCl3 at 20°C according to Scheme 1.a
Repeating unit
Yield (%)b
2-COC
Polymer
n
m
Terminal group
OC
4-COC
p/o ratio
Mass balance (%)c
–
1
2
3
4
5
6
7
–
2
3
3
3
3
3
4
4
4
4
4
5
6
6
6
6
8
8
8
–
–
–
–
–
3
6
–
2
3
4
6
9
12
4
6
8
10
12
5
6
8
10
12
8
10
12
2
–
11.2
–
–
0.7
–
–
–
2.4
–
5.2
3.3
1.2
0.6
5.5
–
11.3
3.3
2.3
3.0
1.8
1.9
2.0
1.7
2.6
3.1
2.6
3.1
2.8
2.2
2.2
2.9
2.8
3.4
3.6
3.5
4.4
3.4
1.8
3.6
5.3
3.2
3.4
76.3
94.9
96.0
96.1
96.0
97.1
96.2
95.5
95.7
91.0
93.3
94.9
96.2
91.6
96.4
95.4
96.4
91.3
92.9
94.7
95.4
95.8
96.2
95.6
92.8
95.8
94.1
6.8
28.7
41.7
32.0
53.3
51.1
48.1
56.2
36.8
29.3
35.9
30.6
34.4
41.6
43.8
32.9
34.4
26.9
25.8
27.1
21.7
28.2
53.4
26.6
17.5
29.9
27.7
98.8
98.2
98.3
99.8
97.8
99.0
98.2
99.6
98.3
99.3
99.2
99.2
99.6
99.3
98.6
98.3
99.2
99.3
99.3
99.2
99.8
99.8
98.0
99.5
99.4
99.5
99.6
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Br
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
–
–
4.6
2.8
1.0
–
0.6
–
0.3
1.3
0.5
2.1
3
4
6
8
6
8
Br
Br
Br
Br
Br
Br
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of OC (10.8 g, 100 mmol), AlCl3 (0.5 g) and 1–26 (0.2 g) at 20°C
over 2 h.
bQuantitative GC was used to calculate the yield (%) of all identified components of the product mixture.
cThe sum of the yields (%) of the identified products, to check whether significant quantities of materials were unaccounted
for.
Next, a range of polymers (5, 7, 12, 14, 21, 23, 25, and 26) that provided high yields of 4-
COC and high para/ortho ratios were chosen to see whether they are equally effective with
smaller quantities of polymer. The para/ortho ratios recorded with three different quanti-
ties (200, 100, and 50 mg) of these polymers are shown in Figure 2. Clearly, the para/ortho
ratio declined in most cases when the quantity of polymer was reduced, but polymer 21 was
exceptional in showing virtually no change in para/ortho ratio as the quantity was reduced
from 200 to 50 mg.
Polymer 21 provided a consistent para/ortho ratio and did not give much poorer results
as the quantity was decreased. Therefore, a more extensive study of the effect of the amount
of polymer 21 used was conducted (Table 2). It should be noted that polymer 21 is also easy
to make and has a higher sulfur content than most of the other polymers. Clearly, the yield
of 4-COC was still high (95.5%) even when a very small quantity of polymer 21 was used
(only 2 mg).
Next, chlorination of MC was investigated under conditions similar to those used in the
chlorination of OC (Scheme 2). The yields of 2-chloro-m-cresol (2-CMC) and 4-CMC are
shown in Table 3. Some improvement in the yield of 4-CMX and para/ortho ratio was seen
when any of the catalysts were used, and in the best cases the yield of 4-CMC increased to

JOURNAL OF SULFUR CHEMISTRY
5
Figure 2. Effect of quantity of polymers on p/o ratio in chlorination of o-cresol.
Table 2. Chlorination of o-cresol using sulfuryl chloride and polymer 21 as a catalyst in the presence of
AlCl3 at 20°C according to Scheme 1.a
Yield (%)b
21 (mg)
AlCl3 (mg)
OC
2-COC
4-COC
p/o ratio
Mass balance (%)c
—
200
200
100
100
50
50
50
50
40
40
30
20
10
10
10
5
500
500
300
500
300
500
300
100
50
100
50
50
50
50
30
20
20
15
15
20
15
10
11.2
0.6
0.6
0.7
0.6
0.4
–
0.4
0.2
–
–
0.2
–
0.2
0.2
–
11.3
3.4
3.5
3.3
3.2
3.4
3.5
3.6
3.7
3.6
3.5
3.6
3.5
3.7
3.9
3.7
3.7
3.9
3.8
4.1
4.2
4.3
76.3
95.8
95.6
95.8
96.0
95.9
96.1
95.9
95.9
96.3
96.3
96.1
96.4
96.0
95.8
95.9
95.7
95.6
95.7
95.6
95.5
95.5
6.8
28.2
27.3
29.0
30.0
28.2
27.5
26.6
25.9
26.7
27.5
26.7
27.5
25.9
24.6
25.9
25.8
24.5
25.2
23.3
22.7
22.2
98.8
99.8
99.7
99.8
99.8
99.7
99.6
99.9
99.8
99.9
99.8
99.9
99.9
99.9
99.9
99.6
99.4
99.5
99.7
99.7
99.7
99.8
–
–
0.2
–
–
5
3
2
2
2
–
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of OC (10.8 g, 100 mmol), AlCl3 and 21 at 20°C for 2 h.
bQuantitative GC was used to calculate the yields (%).
cSum of the yields (%) of the identified products.
94.6% (polymers 7 and 14), from 87.4% in the absence of any catalyst, or the para/ortho
ratio increased to 26.0–27.9 (polymers 17 and 18) from 8.3 in the absence of any catalyst.
Generally, catalysts with shorter spacers (n, m = 2–4) provided lower yields (88.2–91.9%)
than the ones with longer spacers (n, m = 6–12; 90.5–94.6%), but differences in yield of
4-CMC or in selectivity ratio were not dramatic.

6
K. SMITH ET AL.
Scheme 2. Chlorination of m-cresol using sulfuryl chloride and poly(alkylene sulfide)s 1–26.
Table 3. Chlorination of m-cresol using sulfuryl chloride and poly(alkylene sulfide)s 1–26 as catalysts in
the presence of AlCl3 at 20°C according to Scheme 2.a
Repeating unit
Yield (%)b
2-CMC
Polymer
n
m
Terminal group
MC
4-CMC
p/o ratio
Mass balance (%)c
–
1
2
3
4
5
6
7
–
2
3
3
3
3
3
4
4
4
4
4
5
6
6
6
6
8
8
8
–
–
–
–
–
3
6
–
2
3
4
6
9
12
4
6
8
10
12
5
6
8
10
12
8
10
12
2
–
1.6
0.6
2.9
0.5
1.6
3.5
1.6
0.6
2.4
1.9
2.9
2.4
0.3
0.6
0.5
0.6
3.5
2.0
3.9
1.7
1.5
0.4
0.5
0.5
0.4
0.6
0.9
10.5
8.6
7.4
9.0
3.8
5.1
4.7
4.1
4.5
3.9
4.4
4.5
5.3
6.7
4.6
3.9
3.6
3.6
3.3
3.7
8.2
9.0
7.1
6.7
4.1
6.7
4.7
87.4
88.8
88.2
89.7
93.2
90.5
93.2
94.6
92.4
92.3
92.1
92.0
94.2
92.3
94.6
93.6
92.2
93.7
92.1
93.6
89.3
90.1
91.9
92.4
94.0
92.3
93.6
8.3
10.3
11.9
10.0
24.5
17.7
19.8
23.1
20.5
23.7
20.9
20.4
17.8
13.8
20.6
24.0
25.6
26.0
27.9
25.3
10.9
10.0
12.9
13.8
22.9
13.8
19.9
99.5
98.0
98.5
99.2
98.6
99.1
99.5
99.3
99.3
98.1
99.4
98.9
99.8
99.6
99.7
98.1
99.3
99.3
99.3
99.0
99.0
99.5
99.5
99.6
98.5
99.6
99.2
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Br
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
3
4
6
8
6
8
Br
Br
Br
Br
Br
Br
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of MC (10.8 g, 100 mmol), AlCl3 (0.5 g) and 1–26 (0.2 g) at 20°C
over 2 h.
bQuantitative GC was used to calculate the yields (%).
cThe sum of the yields (%) of the identified products.
In view of the lack of clear trends in selectivity, a range of different polymers (4, 5,
6, 14, and 25) was selected to test the effect of their quantities on the para/ortho ratios.
The para/ortho ratios recorded using 200, 100, and 50 mg of these polymers are shown in
Figure 3. Clearly, the para/ortho ratio generally declined when the quantity of polymer was
reduced, but the degree of reduction with polymers 14 and 25 was exceptionally small.
Polymer 25 was even used in a very low amount (5 mg) to provide 4-CMC in 92.1% yield
with a p/o of 13.2, values that are only marginally lower than with 200 mg of that polymer.
It may be possible to identify a polymer that gives even higher values with a very small

JOURNAL OF SULFUR CHEMISTRY
7
Figure 3. Effect of quantity of polymers on para/ortho ratio in chlorination of m-cresol.
Scheme 3. Chlorination of m-xylenol using sulfuryl chloride and poly(alkylene sulfide)s 1–26.
amount of catalyst, but further studies were not justified at this stage. Instead, attention
was turned to chlorination of meta-xylenol.
Since MX does not melt at a low enough temperature, a solvent is needed for its reactions
with sulfuryl chloride in the presence of a polymer catalyst. Furthermore, commercial 4-
CMX has a specification limiting the amount of aluminum permitted. Chlorination of MX
was attempted in the presence of FeCl3 rather than AlCl3 and in DCM, since FeCl3 was
previously used in chlorination of MX using cyclic and polymeric disulfides as catalysts in
DCM [28]. In view of the fact that smaller quantities than 200 mg of some catalysts had
proved very successful with OC and MC, the chlorination of MX (Scheme 3) was initially
attempted at 20°C using only 100 mg of poly(alkylene sulfide)s 1–26 as catalysts. The results
obtained are recorded in Table 4.
The results showed that polymers with longer spacer units (at least five methylene units,
but especially when one of the spacer units was eight methylene groups long) gave higher
yields of 4-CMX and higher para/ortho ratios than those with short spacer units, and that
polymers made using the lithiation method (recorded as having Bu terminal groups; i.e.
polymers 1–19) generally gave higher ratios than those made using the sodium sulfide
method (Br terminal groups; i.e. polymers 20–26), although the latter types have the advan-
tage that they are simpler and cheaper to make. In consequence, we selected several of the
polymer sulfides (namely 14, 17, 23, 24 and 26) for more detailed study. It should be noted

8
K. SMITH ET AL.
Table 4. Chlorination of m-xylenol using sulfuryl chloride and poly(alkylene sulfide)s 1–26 as catalysts
in the presence of FeCl3 in DCM at 20°C according to Scheme 3.a
Repeatingunit
Yield (%)b
Polymer
m
n
Terminal group
MX
2-CMX
4-CMX
DCMX
p/o ratio
Mass balance (%)c
–
1
2
3
4
5
6
7
–
2
3
3
3
3
3
4
4
4
4
4
5
6
6
6
6
6
8
8
8
8
–
–
–
–
–
3
6
–
2
3
4
6
9
12
4
6
8
10
12
5
6
8
–
13.0
0.8
2.2
2.0
0.5
1.1
3.2
1.8
3.1
4.8
1.4
1.4
0.3
1.4
1.0
1.9
2.2
2.4
1.2
1.0
3.8
2.5
0.7
1.8
3.0
1.4
0.8
1.4
0.6
8.7
7.8
6.6
6.8
5.6
4.9
6.7
7.4
10.1
9.3
10.0
7.4
4.7
3.8
3.5
4.0
5.1
4.6
4.1
3.5
4.6
4.0
11.2
8.7
7.1
6.8
5.2
6.8
4.9
78.3
88.4
88.1
90.5
92.7
91.8
89.8
90.3
86.1
85.7
87.7
89.0
94.1
94.4
92.5
93.8
92.4
92.8
94.4
94.2
91.2
93.3
86.3
88.7
89.3
90.8
93.6
90.8
93.6
–
9.03
11.3
13.3
13.3
16.6
18.7
13.4
12.2
8.5
100.0
99.8
99.7
99.9
99.8
99.6
99.7
99.9
99.8
99.8
99.7
99.8
99.9
99.8
99.7
99.7
99.7
99.8
99.7
99.8
99.6
99.8
99.9
99.9
99.9
99.9
99.6
99.9
99.9
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Br
2.8
2.8
0.6
1.0
1.8
–
0.4
0.5
–
0.6
2.0
0.8
0.2
2.7
–
8
9
9.2
8.8
10
11
12
13
14
14d
15
16
17
17e
18
19
20
21
22
23
24
25
26
12.0
20.0
24.8
26.4
23.5
18.1
20.2
23.0
26.9
19.8
23.3
7.70
10.2
12.6
13.3
18.0
13.3
19.1
8
10
12
8
–
–
–
1.1
–
8
10
12
2
3
4
6
8
6
8
–
1.7
0.7
0.5
0.9
–
Br
Br
Br
Br
Br
Br
0.9
0.8
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of MX (12.2 g, 100 mmol), FeCl3 (0.1 g) and 1–26 (0.1 g) in DCM
(50 ml) at 20°C over 2 h.
bQuantitative GC was used to calculate the yields (%).
cThe sum of the yields (%) of the identified products.
dPolymer 14 (50 mg) was used.
ePolymer 17 (50 mg) was used.
that 2,4-dichloro-m-xylenol was produced in most reactions, but in low yield (0–2.8%, See
Table 4).
Several other solvents such as diethyl ether, acetonitrile, 1,2-dichloroethane, chloroform
and toluene were tested as media for the chlorination of m-xylenol, but most of these sol-
vents did not provide high enough yields of 4-CMX or high enough para/ortho selectivity.
However, chlorination of MX in tetrachloroethylene (TCE) provided high yields of 4-CMX
when using the selected catalysts, even with smaller quantities of catalyst. Therefore, the
standard 100 mmol reaction was conducted in TCE in the presence of 30 mg or less of the
selected catalysts, at 20°C. The results obtained are shown in Table 5. Excellent yields of
4-CMX (ca. 97%) were obtained in most cases. Lowering the quantity of catalyst to only
5 mg with polymer 23 still produced 94.9% of the para-product.
A further advantage of TCE is that it can be used at higher temperatures than DCM,
which is preferable for maintaining a concentrated solution during reaction, as would
be desirable for commercial scale application. Therefore, reactions were conducted at 2.5
times higher concentration and at various temperatures (30–60°C), and in some cases the

JOURNAL OF SULFUR CHEMISTRY
9
Table 5. Chlorination of m-xylenol using sulfuryl chloride and poly(alkylene sulfide)s 14, 17, 23, 24, or
26 as catalysts in the presence of FeCl3 in TCE at 20°C according to Scheme 3.a
Yield (%)b
Polymer
(mg)
FeCl3 (mg)
MX
2-CMX
4-CMX
DCMX
p/o ratio
Mass balance (%)c
–
–
100
50
50
50
50
50
25
3.2
0.7
0.3
1.5
0.7
0.5
0.5
9.4
1.4
1.3
2.8
1.1
3.1
3.9
87.0
97.4
97.6
94.9
96.7
96.0
95.2
0.3
0.3
0.4
0.7
1.4
0.3
0.3
9.2
69.6
74.9
33.9
87.9
31.0
24.4
99.9
99.8
99.6
99.9
99.9
99.9
99.9
14
17
23
24
26
26
30
30
5
30
30
10
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of MX (12.2 g, 100 mmol), FeCl3 and appropriate catalyst in TCE
(50 ml) at 20°C over 2 h.
bQuantitative GC was used to calculate the yields (%).
cThe sum of the yields (%) of the identified products.
Table 6. Chlorination of m-xylenol using sulfuryl chloride and poly(alkylene sulfide)s 14, 17, 23, 24, or
26 as catalysts in the presence of FeCl3 in TCE at different temperatures according to Scheme 3.a
Yield (%)b
Polymer
(mg)
FeCl3 (mg)
T (°C)
MX
2-CMX
4-CMX
DCMX
p/o ratio
Mass balance (%)c
14
14
17
17
17
17
23
23
24
24
24
26
26
26
30
30
30
30
30
30
5
10
30
20
30
30
30
15
50
50
50
50
50
50
20
50
50
50
50
50
50
25
50
60
30
40
50
60
40
50
40
50
60
30
40
50
0.7
0.4
0.5
0.3
0.8
0.3
1.6
0.5
1.2
0.6
0.8
0.6
0.5
0.7
4.0
4.3
2.4
3.9
4.0
5.2
3.5
5.0
2.4
4.9
5.2
3.9
4.2
4.3
94.9
95.2
94.9
95.3
95.1
94.4
94.2
94.4
94.6
94.3
93.5
95.1
94.8
94.3
0.3
–
1.9
0.3
–
–
0.6
–
1.3
0.1
0.3
0.3
0.3
0.6
23.7
22.1
39.5
24.4
23.7
18.2
26.9
18.9
39.4
19.2
18.0
24.4
22.6
21.9
99.9
99.9
99.7
99.8
99.9
99.9
99.9
99.9
99.5
99.9
99.8
99.9
99.8
99.9
aSOCl2 (8.9 ml, 110 mmol) was slowly added to a mixture of MX (12.2 g, 100 mmol), FeCl3 and the appropriate catalyst in TCE
(20 ml) over 2 h.
bQuantitative GC was used to calculate the yields (%).
cThe sum of the yields (%) of the identified products.
amount of catalyst was further reduced. The results are shown in Table 6. High yields
(93.5–95.3%) of 4-CMX could still be obtained under the conditions attempted. The results
demonstrate that the temperature, solvent and quantity of both FeCl3 and catalyst can be
manipulated without a large drop in the yield of 4-CMX. This could therefore provide a
useful commercial process and to reinforce that point a reaction was scaled up to 0.5 mol
scale. Chlorination of MX (61 g, 500 mmol) using SO2Cl2 (525 mmol) in TCE (100 ml) at
40°C in the presence of polymer 23 (25 mg) and FeCl3 (75 mg) gave 4-CMX in 94% yield
and 2-CMX in only 4.3% yield (a para/ortho ratio of 21.9).
3. Conclusion
Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chloride in the pres-
ence of poly(alkylene sulfide)s and a Lewis acid provides high yields of the corresponding

10
K. SMITH ET AL.
4-chlorophenols with high para/ortho ratios. For o-cresol, poly(alkylene sulfide)s with
at least one shorter chain (three or four methylene groups between sulfur atoms)
led to somewhat better para/ortho ratios than those obtained with polymers contain-
ing only longer chains (at least six methylene groups between the sulfur atoms). On
the other hand, high yields of both 4-chloro-m-cresol and 4-chloro-m-xyelenol were
obtained when chlorination of m-cresol and m-xylenol was carried out in the presence of
poly(alkylene sulfide)s containing at least one longer spacer group (six methylene groups
or more), whereas the para-selectivity was typically somewhat lower with catalysts hav-
ing shorter spacers (four methylene groups and less). The chlorination processes reported
are highly selective towards para-chlorophenols and have the potential to be applied
commercially.
4. Experimental section
4.1. General
Reagents and solvents were obtained from Sigma-Aldrich Chemical Company. Sulfuryl
chloride was distilled under an inert atmosphere and used freshly. A Shimadzu GC-2014
Gas Chromatograph using a capillary ZB Carbowax column (30, 0.32 mm ID) was used
to analyse components of chlorination reaction mixtures quantitatively using tetradecane
as a standard. The temperature of the column started at 40°C for 3 min, ramped to 220°C
(10°C/min) and held for 10 min. The detector and injector temperatures were 250 and
300°C, respectively.
4.2. General procedure of the chlorination of cresols
To a mixture of melted o-cresol or m-cresol (10.8 g, 100.0 mmol), AlCl3 (0.5 g) and
the appropriate poly(alkylene sulfide) (1–26, 0.2 g), freshly distilled SO2Cl2 (8.9 ml,
110.0 mmol) was slowly added over 2 h. The reaction mixture was stirred for 2 h longer and
then quenched with water (30 ml) and the products were extracted with Et2O (3 × 30 ml).
The organic layers were dried over MgSO4, filtered, and the solvent was removed under
vacuum. The crude product was weighed and analyzed quantitatively by GC. Some reac-
tions had different amounts of polymer catalyst and/or aluminum chloride (see results
section), but were otherwise conducted in the same manner.
4.3. General procedure for the chlorination of m-xylenol
To a stirred mixture of m-xylenol (12.2 g, 100.0 mmol), FeCl3 (0.1 g), and the appropri-
ate poly(alkylene sulfide) (1–26, 0.1 g) in DCM (50 ml), freshly distilled SO2Cl2 (8.9 ml,
110.0 mmol) was slowly added over 2 h and the mixture was stirred for another 2 h. The
mixture was worked up as described for the chlorination of cresols and the product mix-
ture was analyzed by GC. Some reactions were conducted in different solvents, and/or with
different quantities of solvent, polymer and/or ferric chloride (see results section), but were
otherwise conducted in the same manner.

JOURNAL OF SULFUR CHEMISTRY
11
Acknowledgements
A. S. Hegazy thanks Swansea and Cardiff Universities for support. G. A. El-Hiti is grateful to
the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of
Scientific Research Chairs.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This work was supported by King Saud University [Deanship of Scientific Research Chairs].
ORCID
Keith Smith http://orcid.org/0000-0003-4838-5651
Gamal A. El-Hiti http://orcid.org/0000-0001-6675-3126
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