α-chlorination of acetophenones using 1,3-dichloro-5,5- dimethylhydantoin

Article abstract of DOI:10.1080/00397910500334637

A novel method for the synthesis of α-chloroacetophenones using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) and p-toluenesulfonic acid in methanol at 30-35°C is described. Substituted acetophenones at the para position or meta position of aromatic ring give α-chloroacetophenones in high yield. However, reaction of o-nitroacetophenone does not take place under the same condition. Copyright Taylor & Francis LLC.

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α‐Chlorination of Acetophenones Using
1,3‐Dichloro‐5,5‐Dimethylhydantoin
Zijin Xu a , Deyan Zhang, a & Xinzhuo Zou a
a Department of Chemistry, East China Normal University, Shanghai, China
Published online: 15 Aug 2006.
To cite this article: Zijin Xu , Deyan Zhang, & Xinzhuo Zou (2006) α‐Chlorination of Acetophenones
Using 1,3‐Dichloro‐5,5‐Dimethylhydantoin, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:2, 255-258, DOI: 10.1080/00397910500334637
To link to this article: http://dx.doi.org/10.1080/00397910500334637
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Synthetic Communicationsw, 36: 255–258, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500334637
a-Chlorination of Acetophenones Using
1,3-Dichloro-5,5-Dimethylhydantoin
Zijin Xu, Deyan Zhang, and Xinzhuo Zou
Department of Chemistry, East China Normal University,
Shanghai, China
Abstract: A novel method for the synthesis of a-chloroacetophenones using
1,3-dichloro-5,5-dimethylhydantoin (DCDMH) and p-toluenesulfonic acid in methanol
at 30–358C is described. Substituted acetophenones at the para position or meta
position of aromatic ring give a-chloroacetophenones in high yield. However, reaction
of o-nitroacetophenone does not take place under the same condition.
Keywords: Acetophenones, a-chlorination, 1,3-dichloro-5,5-dimethylhydantoin
a-Chloroacetophenones are among the most versatile intermediates used for
medicine and agriculture, and their high reactivity makes them prone to react
with a large number of nucleophiles to provide a variety of useful
compounds.[1] Direct conversion of acetophenones into a-chloroacetophenones
is very important synthetic transformation that has been received considerable
attention. Generally the direct conversion can be accomplished by using
chlorination agents such as copper(II) chloride,[2] sulfuryl chloride, p-toluene-
sulfonyl chloride, N-chlorosuccinimide, tetraethylammonium trichloride,[3]
and chlorine.[4] Chlorine is a kind of common chlorinating agent, but the
low selectivity, strong corrosion of equipment, and strong toxicity make
their utilization ratio limited. 1,3-Dichloro-5,5-dimethylhydantoin (DCDMH)
is a new kind of disinfecting agent and bleaching materials that has been
extensively used for disinfections of industrial and drinking water.
Recently, it was reported that electrophilic aromatic ring chlorination using
Received in Japan May 30, 2005
Address correspondence to Xinzhuo Zou, Department of Chemistry, East China
Normal University, 3663 Zhongshan Road (N), Shanghai 200062, China.
Tel.: 86-21-62233993; Fax: 86-21-62457095; E-mail: xzzou@chem.ecnu.edu.cn
255

256
Z. Xu, D. Zhang, and X. Zou
DCDMH in the presence of p-TsOH has been achieved.[5] However, the report
on the side chain a-chlorination of an acyl arene with DCDMH is rare. In this
communication, we report a convenient side chain a-chlorination of substi-
tuted acetophenones in the DCDMH–acid system (Scheme 1).
Reactions were carried out using an optimized quantity of p-TsOH in
methanol at 30–358C. Compared with the yields of substitution reactions,
high yield for a-chlorination of substituted acetophenones was observed in
the case of a substituent at the para position of aromatic ring (Table 1). It
seems that the reactivity has no relation to the electronic effect. We obtain
good yields whether the substituted group is an electron-donating group
such as methyl or methoxy or an electron-withdrawing group such as nitro
group, chloro, and bromo. But it is likely that the position of the substituent
is very important. Compared to the results of p-nitroacetophenone with the
m-nitroacetophenone, the yield goes down from 84% to 77%, whereas no
reaction take place for the o-nitroacetophenone.
Samant et al. gave the mechanism of keto-enol tautomerism in the
process of the bromination of substituted acetophenones using NBS in the
presence of p-TsOH.[6] They think the conversion from keto-form to
enol-form is the rate-determining step. The results of a-chlorination of
o-, m-, and p-nitroacetophenones support the mechanism. The bulk of
o-nitro group of o-nitroacetophenone hindered the conversion from keto-
form to enol-form, so the reaction does not take place.
Dichlorinated compounds were not isolated in the reaction with DCDMH.
The reason may be related to the reaction mechanism. Samant et al. think
polybromo compounds were not formed in the process of bromination of sub-
stituted acetophenones using NBS in the presence of p-TsOH.[6] The reaction
mechanism may be similar with the bromination using NBS. On the other
hand, DCDMH was slowly dropping and the reaction was carried out at
lower temperature, which may aid the yield of a,a-dichloroacetophenone.
In conclusion, a-chlorination of substituted acetophenones using
DCDMH, which is an available and cheap industrial product, is a novel and
efficient method. The advantages of the present method is the ease of manipu-
lation, high recovery rate, and formation of cleaner products under mild
reaction conditions. Also, DMH is recyclable, reducing pollution and satisfy-
ing the requirement of green chemistry.
Scheme 1.

a-Chlorination of Acetophenones
257
Table 1. Results of reaction of substituted acetophenones with
DCDMHa
Reactant
Product
Yieldb
Mp (lit.)
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
78%
84%
94%
92%
93%
84%
77%
0
50–538C (51–528C)[7]
51–548C (54.5–558C)[8]
92–948C (96–988C)[9]
98–1018C (101–101.58C)[10]
114–1168C (116–1178C)[11]
88–918C (90–918C)[12]
100–1028C (100.5–1028C)[13]
1g
1h
3g
3h
aReactions were carried out at 30–358C for 8 h in methanol; the
molar ratio of acetophenone, DCDMH, and p-TsOH is 1 : 0.75 : 0.5.
bIsolated yield.
GENERAL EXPERIMENTAL PROCEDURE
A model reaction was run as follows. Acetophenone 1.21 g (10 mmol) and
p-TsOH 0.95 g (5 mmol) in 5 mL of methanol was added to a 50-mL flask
and stirred. A solution of 1.48 g (7.5 mmol) of DCDMH in 25 mL of
methanol was added from the dropping funnel over an hour at 30–358C.
After the addition, the mixture was stirred at 30–358C for 8 h. The progress
of the reaction was monitored by TLC. The solvent was distilled off under
reduced pressure to afford the crude product. The crude product was
washed by 50 mL of ice water. After it was filtered and dried, 1.2 g of the
crude crystals were obtained: yield 78%; mp 50–538C (lit 52–568C).
1H NMR (500 MHz, CDCl3): d 4.72 (2H, s, CH2Cl), 7.51 (2H, t,
J ¼ 7.8 Hz, ArH), 7.63 (1H, t, J ¼ 7.4 Hz, ArH), 7.96–7.98 (2H, m, ArH).
Sodium carbonate was added to the filtrate to neutralize the p-TsOH. Water
was removed under reduced pressure. The residue was extracted with
several portions of acetone, and the combined acetone layers were dried.
After removal of the acetone, DMH was recovered.
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