Selective ortho-chlorination of phenol using sulfuryl chloride in the presence of t-butylaminomethyl polystyrene as a heterogeneous amine catalyst

Article abstract of DOI:10.1016/j.tetlet.2004.09.102

ortho-Chlorination of phenol with sulfuryl chloride in the presence of a t-butylaminomethyl polystyrene catalyst, proceeds in high conversion (～98%) and with high selectivity (～89%). Reaction of phenol with sulfuryl chloride in the presence of a catalytic amount of the heterogeneous amine catalyst, t-butylaminomethyl polystyrene, in a nonpolar solvent, proceeds with high conversion (～98%) and with high selectivity (～89%) to ortho-chlorophenol. The catalyst is stable under the chlorination conditions, and can easily be regenerated by filtration and reused. This method could be applicable to other phenols.

Full text of DOI:10.1016/j.tetlet.2004.09.102

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8471–8473
Selective ortho-chlorination of phenol using sulfuryl chloride in
the presence of t-butylaminomethyl polystyrene as a heterogeneous
amine catalyst
Jallal M. Gnaima,* and Roger A. Sheldonb
aDepartment of Chemistry, The Triangle Regional R&D Center, PO Box 2167, Kfar-Qari 30075, Israel
bDepartment of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands
Received 18 August 2004; revised 9 September 2004; accepted 13 September 2004
Available online 30 September 2004
Abstract—Reaction of phenol with sulfuryl chloride in the presence of a catalytic amount of the heterogeneous amine catalyst,
t-butylaminomethyl polystyrene, in a nonpolar solvent, proceeds with high conversion (ꢀ98%) and with high selectivity (ꢀ89%)
to ortho-chlorophenol. The catalyst is stable under the chlorination conditions, and can easily be regenerated by filtration and
reused. This method could be applicable to other phenols.
Ó 2004 Elsevier Ltd. All rights reserved.
Electrophilic aromatic halogenation1,2 reactions are of
considerable importance in the production of agrochemi-
cals, pigments, drugs, pharmaceuticals and photographic
materials.3 Chlorination of phenol is a particularly
important reaction, since many chlorophenols are useful
intermediates for the manufacture of insecticides, dye-
stuffs, preservatives and disinfectants.4,5 Traditional
methods of aromatic chlorination involve the use of
acidic reagents that can lead to separation difficulties
and unacceptable levels of toxic and corrosive waste.6
In addition, such reactions are subject to problems
of both chemo- and regioselectivity, generally giving
mixtures of mono-, di- and tri-chlorinated products.7
aminomethyl polystyrene, for the regioselective ortho-
chlorination of phenol.
Several commercial solid amine materials, for example,
amino silica gel, n-propylamino glass and methyl poly-
styrene–NH4Cl resin, were tested in the chlorination of
phenol using SO2Cl2 in toluene at 70°C for 1h. The
results are summarized in Table 1. The o/p ratios
obtained are low and very similar to those obtained with
silica gel as a catalyst under identical conditions. An
improvement in the selectivity of the reaction was
achieved by using aminomethyl polystyrene (amino-
MPS) catalyst (run 5), where the o/p ratio was increased
about twofold compared to the control reaction (run 1).
The available methods for direct ortho-chlorination of
phenol involve the use of t-butyl hypochloride,8–12 N,N-
dichloro-t-butylamine,13 N-chloroamines/silica gel,14
and Cl2 catalyzed by amines.15 Recently,16 we have
reported the liquid phase ortho-chlorination of phenol
using SO2Cl2 catalyzed by secondary amines. The reac-
tion is fast, specific for monochlorination and highly
regioselective for ortho-substitution.17 Herein, we report
an efficient and reusable amine-based catalyst, t-butyl-
Interestingly, the o/p ratio was increased from 2.02 to
2.20, by decreasing the amount of the amino-MPS cata-
lyst from 0.50g to 0.01g (runs 5 and 6), and the o/p ratio
was increased from 2.02 to 2.73, by decreasing the
degree of divinylbenzene cross linked units from 2% to
1% (runs 5 and 7). Although, the cross linking in the cat-
alyst reduces the ortho selectivity of the chlorination,
nevertheless, a certain degree of cross linking in the poly-
styrene structure is an essential factor in order to
enhance the stability of the catalyst, and to diminish
its solubility in organic solvents, and therefore retain
its heterogeneous properties.
Keywords: Chlorination; Catalysis; Phenols; Chlorophenols; Sulfuryl
chloride; Amine; Regioselectivity; Heterogeneous catalyst; Amino-
methyl polystyrene.
*
When the chlorination of phenol was conducted homo-
geneously in the presence of a catalytic amount of
Corresponding author. Tel.: +972 4 638 4650; fax: +972 4 638
4647; e-mail: Jallal_g@zahav.net.il
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.102

8472
J. M. Gnaim, R. A. Sheldon / Tetrahedron Letters 45 (2004) 8471–8473
Table 1. Chlorination of phenol with sulfuryl chloride in the presence of various catalystsa
OH
OH
Cl
Cl
Cl
Cl
OH
OH
2
4
Cl
Cl
OH
OH
1
Cl
6
Cl
Cl
3
5
Run no.
Catalystb
Amount of catalyst, g
Yield, mol%
4 + 5 + 6
1
2
3
o/p Ratio
1
None
Amino silica gel
Aminopropyl glass
—
92.8
7.5
4.5
19.5
6.8
10.5
5.0
94.0
4.8
5.1
4.1
2.1
2.5
3.0
2.6
2.9
3.8
3.4
47.0
47.8
40.7
29.2
26.9
24.2
2.4
Traces
2.1
2.7
1.12
0.92
2
0.50
0.50
0.50
0.50
0.01
0.50
0.50
0.50
0.50
0.50
0.50
0.10
0.10
0.10
0.10
43.4
45.0
37.7
59.0
59.1
66.1
3.6
3
0.94
0.93
4
Polystyrene methyl–NH4Cl
Amino-MPS (2% DVB)
Amino-MPS (2% DVB)
Amino-MPS (1% DVB)
Chloro-MPS (2% DVB)
N-di(s-butyl)amino-MPSc
N-s-Butylamino-MPS
2.1
5.0
5
2.02
2.20
6
3.5
4.7
7
2.73
1.48
8
Traces
4.0
5.6
9
69.6
68.3
70.8
85.9
86.3
85.4
86.6
85.1
21.6
21.0
17.6
8.2
3.22
3.25
10
11
12
13
14
15
16
N-n-Butylamino-MPS
N-t-Butylamino-MPS
N-t-Butylamino-MPS
7.5
3.8
4.02
10.48
13.08
12.94
12.74
13.09
6.6
6.6
4.6
5.0
Recycled catalyst from run 13
Recycled catalyst from run 14
Recycled catalyst from run 15
6.8
6.5
4.0
5.5
a Chlorination of phenol: To a mixture of phenol (12.6mmol), toluene (87g) and the appropriate solid catalyst (0.01 or 0.1 or 0.5g) gently stirred in
250mL round bottom flask, was added SO2Cl2 (12.6mmol) dropwise at 70°C. The mixture was stirred at this temperature for 1h. The solid catalyst
was filtered off, volatile solvents were removed under vacuum and the residue was analyzed by GLC. The GLC analyses were performed with a
Hewlett Packard instrument equipped with a F.I.D. coupled to a Perkin–Elmer GP100 recorder. A glass column (50m, 0.53mm i.d.) was packed
with CP sil 5 CB (2.0lm). Yields, given in mol percent, determined with 1,2-dichlorobenzene as an internal standard.
b Amino silica gel and n-propylamino glass were supplied by Macherey-Nagel Co. Aminomethyl polystyrene (amino-MPS) and chloromethyl
polystyrene (chloro-MPS) were supplied by Fluka. Amino-MPS (2% DVB) and amino-MPS (1%) polymers contain 1.1 and 0.6mmol amine/1g,
respectively. Chloro-MPS (2%) polymer contains 0.7mmol chlorine/1g.
c Preparation of N-alkylaminomethyl polystyrene catalyst: To a mixture of K2CO3 (1.0g), amine (1mL) and dry DMF (10mL), was added chloro-
methyl polystyrene (1g). The reaction mixture was heated overnight at 50°C. The solid was filtered, washed with 20mL portions of dichloro-
methane, acetone, water, 8% NaOH solution, water and finally with acetone. The resulting solid was dried overnight under vacuum.
benzylamine, an o/p ratio of 1.75 was obtained. Using a
secondary amine, N-methylbenzylamine, a significant
enhancement of the ortho selectivity was observed, that
is, o/p ratio of 14.51. We found these results promising
enough for further study, and therefore, further struc-
tural modification of the amino group in the solid
amino-MPS catalyst has been investigated.
rial chloro-MPS is 10 times less expensive than amino-
MPS.
We have prepared several modified N-butylamino-MPS
catalysts, for example, n-butyl-, s-butyl-, di-s-butyl- and
t-butylamino-MPS by reaction of the appropriate amine
with chloro-MPS in a K2CO3/DMF suspension. The
chlorination results using these modified catalysts are
presented in Table 1. The observed o/p ratios for n-
butyl-, s-butyl-, di-s-butyl- and t-butylamino-MPS are
4.02, 3.25, 3.22 and 10.48, respectively.
Preparation of secondary amine derivatives of the
methyl polystyrene resin can be achieved by reaction
of amino-MPS with alkyl halides, or by reaction of chlo-
romethyl polystyrene (chloro-MPS) with alkyl amine.
We preferred the second approach for the following rea-
sons: (i) the benzyl chloride group present in chloro-
MPS is more reactive towards nucleophilic substitution
than that of alkyl halides, (ii) one possible product can
be formed according to the first approach, however, a
mixture of products (secondary, tertiary and quaternary
amines) may be formed by reaction of amino-MPS
with alkyl halides and (iii) the commercial starting mate-
By conducting the reaction with a reduced amount of
the t-butylamino-MPS catalyst, a further improvement
in the o/p ratio was achieved, that is, o/p ratio of 13.08
(run 13). The heterogeneous t-butylamino-MPS catalyst
was recycled three times, without any special treatment,
and the chlorination results showed clearly that the cat-
alyst is very stable under SO2Cl2 chlorination condi-
tions, and retained its catalytic activity (runs 14–16).

J. M. Gnaim, R. A. Sheldon / Tetrahedron Letters 45 (2004) 8471–8473
8473
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The results with t-butylamino-MPS are similar to those
obtained with homogeneous amine catalysts, and con-
firm our previous observation 16 that, secondary amines
with bulky substituents are excellent catalysts for regio-
selective ortho-chlorination of phenol in a nonpolar
medium. Preliminary results show that this method
could be applicable to other phenolic compounds.
Under similar conditions using N-bromosuccinimide
(NBS) in the presence of t-butylamino-MPS catalyst,
selective ortho-bromination of phenol was achieved.18
Therefore, it will be of great interest to test this catalyst
in other amine catalyzed reactions.
Acknowledgements
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We thank Coalite Chemicals, UK, and J.M.G. thanks
the Ministry of Science and Technology in Israel for
financial support for this work.
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References and notes
1. De la Mare, P. B. Electrophilic Halogenation; Cambridge
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17. Sakaguchi, H.; Matsuo, S. U.S. Patent 6,635,787,B3, 2003.
18. Gnaim, J. M.; Sheldon, R. A., unpublished results.