A safe, convenient and efficient one-pot synthesis of α-chloroketone acetals directly from ketones using iodobenzene dichloride

Article abstract of DOI:10.1055/s-0029-1216856

Various ketones, including aliphatic and aromatic ketones, can be directly converted into their corresponding α-chloroketone acetals in high to excellent yields using iodobenzene dichloride in ethylene glycol in the presence of 4 A molecular sieves at room temperature. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216856

2324
PAPER
A Safe, Convenient and Efficient One-Pot Synthesis of a-Chloroketone Acetals
Directly from Ketones Using Iodobenzene Dichloride
One-pot
S
u
ynthesis of
a
n
-Chloroketone
Ace
Y
tals u, Chi Zhang*
The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
Fax +86(22)23499247; E-mail: zhangchi@nankai.edu.cn
Received 22 January 2009; revised 19 March 2009
dichloride for the introduction of elemental chlorine into
Abstract: Various ketones, including aliphatic and aromatic ke-
tones, can be directly converted into their corresponding a-chlo-
roketone acetals in high to excellent yields using iodobenzene
dichloride in ethylene glycol in the presence of 4 Å molecular sieves
at room temperature.
a range of metal complexes have also been described.10
Iodobenzene dichloride has also been employed to facili-
tate the a-chlorination of ketones in various organic sol-
vents, including acetic acid, acetonitrile, and toluene, to
afford the corresponding a-chlorocarbonyl compounds.11
Herein, as part of our ongoing program on the exploration
of new reactivity of iodobenzene dichloride,12 we present
a safe, convenient and highly efficient one-pot procedure
for the synthesis of a-chloroketone acetals directly from
various ketones using iodobenzene dichloride in ethylene
glycol in the presence of 4 Å molecular sieves at room
temperature.
Key words: ketones, iodobenzene, dichloride, halogenation, hy-
pervalent iodine, acetals
a-Chloroketone acetals are valuable synthetic intermedi-
ates in organic synthesis.1 For example, nucleophilic sub-
stitution reaction of a-chlorocyclohexanone acetal with
nucleophiles such as allyltrimethylsilane, in the presence
of a Lewis acid, has been reported.1a Furthermore, dehy-
drochlorination of a-chloroketone acetals provides a reli-
able way to produce a,b-unsaturated ketones.1c–e Usually,
a-chloroketone acetals are prepared from ketones via two
separate steps, that is, the a-chlorination of ketones2 fol-
lowed by the acetalization of the resulting a-chloroke-
tones.3 The use of molecular chlorine for the direct
conversion of acetone into the cyclic ketal of chloroace-
tone in ethylene glycol has been repoted,4 however, since
chlorine is a toxic gas and difficult to handle safely, this
method has not gained widespread use in organic synthe-
sis. Therefore, it is highly desirable to develop a safe, sim-
ple, easy to handle, and efficient protocol with which to
transform various ketones directly into their correspond-
ing a-chloroketone acetals.
When cyclohexanone was subjected to treatment with 1.1
equivalents of iodobenzene dichloride in methanol at
room temperature, it was interesting to find that 2-chloro-
1,1-dimethoxycyclohexane was formed in 96% yield after
30 minutes. Similarly, treatment of cyclopentanone under
the same reaction conditions resulted in the formation of
2-chloro-1,1-dimethoxycyclopentane in a yield of 96%,
again after 30 minutes. However, other ketones such as
cycloheptanone, indan-1-one and a-tetralone gave only
the corresponding a-chlorination products, 2-chlorocy-
cloheptanone, 2-chloro-2,3-dihydroinden-1-one and 2-
chloro-3,4-dihydronaphthalen-1(2H)-one, in 80%, 94%
and 94% yield, respectively; in order to obtain their corre-
sponding a-chloroketone acetals directly, two changes
were made to the initial procedure. These adjustments
were based on an understanding of working mechanism
involved in the formation of 2-chloro-1,1-dimethoxycy-
clohexane directly from cyclohexanone (Scheme 1).
Iodobenzene dichloride (PhICl2), the first reported hyper-
valent iodine reagent, was synthesized by C. Willgerodt in
1886.5 Because of its low toxicity and ease of handling, it
has been mainly used to replace molecular chlorine as a
chlorinating reagent in organic synthesis.6 For example,
Garvey et al. first observed that the reaction of iodoben-
zene dichloride with unsaturated hydrocarbons in reflux-
ing ethylene dichloride gave the same products as chlorine
addition.7 One example was given for an aromatic substi-
tution reaction in which iodobenzene dichloride was suc-
cessfully applied to chlorinate p-aminoacetophenone on a
large scale.8 Moreover, Breslow et al. have shown beauti-
ful examples of template-directed chlorination of an inac-
tivated C–H bond in steroids using iodobenzene
dichloride.9 Numerous applications of iodobenzene
Firstly, electrophilic addition of iodobenzene dichloride
to the enol form of cyclohexanone gave the intermediate
1, which lost hydrochloric acid to yield intermediate 2.
Nucleophilic attack of a chloride anion on the a-carbon
bearing the iodine(III) structural unit in 2, yields the a-
chloroketone with concomitant reductive elimination of
iodobenzene and the formation of hydrochloric acid. The
generated hydrochloric acid not only promotes the forma-
tion of the enol form of cyclohexanone but also catalyzes
the formation of acetals in alcohols such as methanol.
During acetalization of the 2-chlorocyclohexanone, one
equivalent of water is produced. Since it is known that ac-
etal functionality can be removed in the presence of water
under acidic conditions, we therefore added 4 Å molecu-
lar sieves to the reaction mixture in order to remove the
generated water. Furthermore, in order to produce more
SYNTHESIS 2009, No. 14, pp 2324–2328
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x.
x
x
.
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0
0
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Advanced online publication: 29.05.2009
DOI: 10.1055/s-0029-1216856; Art ID: F02709SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of a-Chloroketone Acetals
2325
of the corresponding a-chloroketone acetal, a much long-
er reaction time was required (2 h) owing to the difficulty
of generating the enol form of pentan-3-one compared
with other tested ketones (entry 9).
••
OH
O
+OH
Cl
I–
(1)
Cl
Cl
Table 1 Substrate Scopea
I
1
Cl
Entry
Products
Time (min)
30
Yield (%)b
92
O
I
O
Cl
I
O
O
Cl
+
– HCl
Cl
Cl
1
Cl–
2
Me
+OH
O
O
2
30
30
86c
80
+OH
O
HO
Cl
Cl
Cl
+
HCl
(2)
••
MeOH
••
O
O
••
MeOH
••
Cl
3d
Me
O
Me
O
Me
Me
H2O+
O
O
+
Cl
– H+
Cl
Cl
– H2O
O
O
4
5
30
30
82
95
Scheme 1 Working mechanism
Cl
stable cyclic acetals, ethylene glycol was employed in
place of methanol. Both changes were assumed to guaran-
tee the formation of a-chloroketone acetal. Gratifyingly,
after these two changes were made, we found that the re-
action system PhICl2/ethylene glycol/4 Å molecular
sieves could directly convert cycloheptanone into its cor-
responding a-chloroketone acetal, 6-chloro-1,4-dioxa-
spiro[4.6]undecane, in an excellent yield within 30 min-
utes (Scheme 2).
O
O
Cl
O
O
6
30
30
85
Cl
Cl
O
O
7e
70c
O
O
O
Cl
PhICl2 (1.1 equiv)
Cl
ethylene glycol
4 Å MS
r.t., 0.5 h
92 %
O
O
8f
9
30
74c
72c
Cl
Scheme 2 One representative example for the syntheses of a-chlo-
roketone cyclic acetals from ketones
Cl
O
Other cyclic ketones such as cyclopentanone and cyclooc-
tanone were also tested; their corresponding a-chloroke-
tone acetals were obtained in high yields in 30 minutes
(Table 1, entries 2 and 3). Aromatic ketones were good
substrates under the present reaction conditions. In the
case of acetophenone, the reaction gave the corresponding
a-chloroacetophenone acetal in 82% yield within 30 min-
2 h
O
a Reactions were conducted with 1 mmol of the ketone and 5 mL of
solvent, under the conditions shown in Scheme 2.
b Isolated yield.
c GC yield.
utes (entry 4). Similar results were obtained for 4¢-methyl- d The yield of the minor product 2-chlorocyclooctanone was 10%.
acetophenone and 4¢-chloroacetophenone (entries 5 and
6). Cyclic aromatic ketones such as indan-1-one and a-te-
tralone, gave the corresponding a-chloroketone acetals in
70% and 74% yield, respectively, in 30 minutes (entries 7
and 8). When the reaction of an aliphatic ketone, pentan-
e The yield of the minor product 2-chloro-2,3-dihydroinden-1-one
was 18%.
f The yield of the minor product 2-chloro-3,4-dihydronaphthalen-
1(2H)-one was 25%.
Though it has been reported that chlorination of acetone
by molecular chlorine in ethylene glycol gave the cyclic
3-one, was examined under these reaction conditions, it
was found that although the reaction afforded a good yield
Synthesis 2009, No. 14, 2324–2328 © Thieme Stuttgart · New York

2326
J. Yu, C. Zhang
PAPER
ketal of chloroacetone as the only product,4 4¢-methylace-
tophenone, which was an excellent substrate under our
Yield: 162 mg (82%); colorless oil.
1H NMR (300 MHz, CDCl3): d = 3.76 (s, 2 H), 3.89–3.94 (m, 2 H),
conditions (Table 1, entry 5), performed poorly under the 4.17–4.21 (m, 2 H), 7.35–7.41 (m, 3 H), 7.50–7.54 (m, 2 H).
reported conditions,4 with very low yields of the desired
cyclic ketal of the chloroketone (Scheme 3).13 This result
indicated that, in some cases,8,14 including the case de-
scribed here, iodobenzene dichloride showed superior re-
activity to that of molecular chlorine in terms of both
chemical yield and selectivity.
13C NMR (75 MHz): d = 49.36, 65.77, 107.86, 125.96, 128.23,
128.72, 139.70.
2-Chloro-1,1-dimethoxycyclohexane1a
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.30–1.37 (m, 1 H), 1.45–1.50 (m,
1 H), 1.60–1.62 (m, 1 H), 1.65–1.72 (m, 1 H), 1.74–1.79 (m, 2 H),
1.88–1.94 (1 H), 1.96–2.08 (m, 1 H), 3.20 (s, 3 H), 3.24 (s, 3 H),
4.21 (br s, 1 H).
O
O
Cl2 (1.1 equiv)
O
13C NMR (75 MHz, CDCl3): d = 19.34, 21.85, 26.79, 31.26, 47.07,
48.08, 59.24, 100.29.
ethylene glycol (15 mL)
r.t., 19 h
Cl
2.55 mmol
conversion: 51%
yield: 19%
2-Chloro-1,1-dimethoxycyclopentane
Colorless oil.
Scheme 3 Treatment of 4¢-methylacetophenone with chlorine gas
IR (KBr): 2960, 2832, 1468, 1437, 1333, 1174, 1122, 1082, 1049,
962, 823, 721, 553 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.61–1.69 (m, 1 H), 1.87–1.98 (m,
4 H), 2.26–2.32 (m, 1 H), 3.24 (s, 3 H), 3.31 (s, 3 H), 4.13 (d,
J = 4.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 18.89, 28.98, 33.57, 48.98, 50.42,
62.13, 111.12.
In conclusion, the reported hypervalent iodine reagent –
iodobenzene dichloride – was found to effect the direct
conversion of various ketones into their corresponding a-
chloroketone acetals in high to excellent yields. Iodoben-
zene dichloride can be prepared in quantitative yield in
five minutes by reacting iodobenzene with sodium hy-
pochlorite in a dilute hydrochloric acid solution at room
temperature.12a The readily availability of iodobenzene
dichloride, as well as its low toxicity and ease of handling
Anal. Calcd for C7H13ClO2: C, 51.07; H, 7.96. Found: C, 50.82; H,
7.78.
compared with those of molecular chlorine, make the 2-Chlorocycloheptanone15
Colorless oil.
present PhICl2/ethylene glycol system an attractive alter-
native method for the effective synthesis of a-chloroke-
tone acetals.
1H NMR (300 MHz, CDCl3): d = 1.19 (s, 1 H), 1.42–1.65 (m, 3 H),
1.80–1.95 (m, 3 H), 2.12–2.22 (m, 1 H), 2.42–2.51(m, 1 H), 2.66–
2.75 (m, 1 H), 4.36 (q, J = 4.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 24.03, 25.85, 28.87, 34.24, 40.13,
63.98, 206.21.
Iodobenzene dichloride was prepared according to the method de-
veloped in our lab.12a Ethylene glycol was dried over anhydrous
MgSO4, then distilled under reduced pressure and stored over 4 Å
molecular sieves. 1H NMR spectra were recorded at 300 MHz and
13C NMR spectra at 75 MHz, using a Bruker AV300 instrument;
CDCl3 was used as solvent. IR spectra were recorded on an FT-IR
spectrometer (Bruker Equinox55) using KBr pellets. GC analyses
were carried out on a Shimadzu 2014 series GC system equipped
with an Rtx-5 column (30 m, ID 0.25 mm) and an FID; injector tem-
perature = 250 °C, detector temperature = 300 °C. N2 was used as
the carrier gas, flow rate 3.0 mL/min. Temperature program: initial
isothermal period of 3.0 min at 100 °C, then an increase at 10.0 °C/
min to 250 °C with an isothermal period of 1 min at 250 °C. High-
resolution mass spectral analyses (HRMS) were performed on a
high-resolution APCI–FTICR mass spectrometer (Varian 7.0 T).
Elementary Analyses were carried out on an Elemental Vario EL
analyzer. Petroleum ether (PE), where used, had a boiling range 60–
90 °C.
2-Chloroindan-1-one16
Pale-yellow oil.
1H NMR (300 MHz, CDCl3): d = 3.31 (dd, J = 3.9, 17.4 Hz, 1 H),
3.79 (dd, J = 7.8, 17.4 Hz, 1 H), 4.57 (dd, J = 3.9, 7.8 Hz, 1 H), 7.45
(t, J = 8.1 Hz, 2 H), 7.65–7.70 (m, 1 H), 7.85 (d, J = 7.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 37.40, 55.62, 124.80, 126.32,
128.19, 133.67, 135.95, 150.64, 199.05.
2-Chloro-1-tetralone17
White Solid; mp 103–105 °C.
1H NMR (300 MHz, CDCl3): d = 2.41–2.52 (m, 1 H), 2.54–2.64 (m,
1 H), 2.95–3.05 (m, 1 H), 3.25–3.35 (m, 1 H), 4.64 (dd, J = 3.9, 7.5
Hz, 1 H), 7.29–7.38 (m, 2 H), 7.50–7.55 (m, 1 H), 8.09 (d, J = 7.2
Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 26.22, 32.35, 59.75, 127.02,
Synthesis of a-Chloroketone Acetals; Typical Procedure
To a solution of acetophenone (120 mg, 1 mmol) in anhydrous eth-
ylene glycol (5 mL) in a 10 mL round-bottom flask, was added 4 Å
MS and iodobenzene dichloride (302 mg, 1.1 mmol). The reaction
was stirred at r.t. and monitored by TLC. After 30 min, the resulting
mixture was diluted with EtOAc (50 mL) and washed with sat. aq
NaHCO3 (5 mL) and sat. aq Na2S2O3 (5 mL). The combined aque-
ous phase was extracted with EtOAc (20 mL) and the combined or-
ganic layer was washed with brine (20 mL), dried over anhydrous
Na2SO4 and concentrated in vacuo to afford the crude product,
which was purified by flash column chromatography (PE–EtOAc,
9:1) to give 2-chloromethyl-2-phenyl[1,3]dioxolane.
128.42, 128.66, 130.39, 134.05, 143.05, 190.72.
6-Chloro-1,4-dioxaspiro[4.6]undecane (Table 1, Entry 1)1c
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.58–2.07 (m, 10 H), 3.93–4.10
(m, 5 H).
13C NMR (75 MHz, CDCl3): d = 20.37, 23.33, 26.03, 31.95, 34.76,
65.02, 65.45, 66.74, 111.14.
6-Chloro-1,4-dioxaspiro[4.4]nonane (Table 1, Entry 2)1d
Colorless oil.
Synthesis 2009, No. 14, 2324–2328 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of a-Chloroketone Acetals
2327
1H NMR (300 MHz, CDCl3): d = 1.67–1.77 (m, 1 H), 1.80–2.00 (m,
3 H), 2.06–2.14 (m, 1 H), 2.21–2.28 (m, 1 H), 3.96–4.10 (m, 5 H).
2¢-Chloro-3¢,4¢-dihydro-2¢H-spiro([1,3]dioxolane-2,1¢-naphtha-
lene) (Table 1, entry 8)
Pale-yellow oil.
13C NMR (75 MHz, CDCl3): d = 18.73, 32.11, 33.02, 62.81, 64.98,
65.47, 116.18.
IR (KBr): 2968, 2895, 2674, 2295, 1958, 1932, 1832, 1700, 1605,
1484, 1442, 1342, 1311, 1232, 1158, 1026, 942, 868, 758, 663, 611,
568, 511, 458 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.30–2.42 (m, 1 H), 2.45–2.55 (m,
1 H), 2.81–2.91 (m, 1 H), 3.06–3.17 (m, 1 H), 4.22–4.33 (m, 4 H),
4.37 (dd, J = 3.0, 7.8 Hz, 1 H), 7.11–7.14 (m, 1 H), 7.21–7.30 (m,
2 H), 7.49–7.52 (m, 1 H).
a-Chlorocyclooctanone Acetal (Table 1, Entry 3)
Colorless oil.
IR (KBr): 2926, 2684, 1726, 1642, 1447, 1332, 1158, 1084, 1032,
953, 853, 784, 716, 658, 505 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.52–1.73 (m, 8 H), 1.78–1.86 (m,
1 H), 1.95–2.03 (m, 1 H), 2.08–2.23 (m, 2 H), 3.94–4.01 (m, 2 H),
4.10–4.14 (m, 2 H), 4.40 (dd, J = 3.0, 8.7 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 25.86, 29.11, 61.39, 66.23, 66.38,
106.69, 126.11, 126.36, 128.42, 128.80, 135.53, 136.22.
13C NMR (75 MHz, CDCl3): d = 22.04, 25.10, 25.64, 27.41, 33.37,
HRMS (APCI): m/z [M + H]+ calcd for C12H13ClO2: 225.0677;
34.03, 65.30, 65.63, 66.12, 111.17.
found: 225.0682.
HRMS (APCI): m/z [M + H]+ calcd for C10H17ClO2: 205.0990;
found: 205.0997.
2-(1-Chloroethyl)-2-ethyl-1,3-dioxolane (Table 1, Entry 9)
Colorless oil.
2-Chloromethyl-2-phenyl[1,3]dioxolane (Table 1, Entry 4)3b
Colorless oil.
IR (KBr): 2981, 2939, 2885, 1454, 1377, 1196, 1157, 1066, 930,
783, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.76 (s, 2 H), 3.89–3.94 (m, 2 H),
4.17–4.21 (m, 2 H), 7.35–7.41 (m, 3 H), 7.50–7.54 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 49.36, 65.77, 107.86, 125.96,
128.23, 128.72, 139.70.
1H NMR (300 MHz, CDCl3): d = 0.93 (t, J = 7.5 Hz, 3 H), 1.50 (d,
J = 6.9 Hz, 3 H), 1.68–1.81 (m, 1 H), 1.88–2.00 (m, 1 H), 4.00–4.11
(m, 5 H).
13C NMR (75 MHz, CDCl3): d = 7.18, 19.68, 26.87, 60.18, 66.22,
66.38, 111.73.
2-Chloromethyl-2-p-tolyl-1,3-dioxolane (Table 1, Entry 5)18
Anal. Calcd for C7H13ClO2: C, 51.07; H, 7.96. Found: C, 50.88; H,
8.22.
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 3 H), 3.75 (s, 2 H), 3.87–
3.95 (m, 2 H), 4.13–4.23 (m, 2 H), 7.18 (d, J = 5.7 Hz, 2 H), 7.40
(d, J = 5.7 Hz, 2 H).
Acknowledgment
13C NMR (75 MHz, CDCl3): d = 21.13, 49.38, 65.72, 107.89,
125.91, 128.95, 136.70, 138.60.
This work was financially supported by The National Natural Sci-
ence Foundation of China (No. 20572046 and No. 20872064) and
the Program for New Century Excellent Talents in University
(NCET-07-0461).
2-Chloromethyl-2-(4-chlorophenyl)-1,3-dioxolane (Table 1, En-
try 6)
White solid; mp 59–60 °C.
References
IR (KBr): 2958, 2895, 2853, 2284, 2053, 1916, 1874, 1800, 1642,
1600, 1479, 1437, 1389, 1295, 1221, 1174, 1079, 1026, 953, 826,
758, 689, 637, 511, 474 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.72 (s, 2 H), 3.88–3.92 (m, 2 H),
4.16–4.20 (m, 2 H), 7.34 (d, J = 6.3 Hz, 2 H), 7.46 (d, J = 6.3 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 49.16, 65.86, 107.59, 127.57,
128.48, 134.81, 138.27.
HRMS (APCI): m/z [M + H]+ calcd for C10H10Cl2O2: 233.0131;
(1) (a) Billings, S. B.; Woerpel, K. A. J. Org. Chem. 2006, 71,
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(2) (a) For sulfuryl chloride as a chlorinating reagent, see:
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1956. (b) For cupric chloride as a chlorinating reagent, see:
Kochi, J. K. J. Am. Chem. Soc. 1955, 77, 5274. (c) For p-
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found: 233.0129.
2¢-Chloro-2¢,3¢-dihydrospiro([1,3]dioxolane-2,1¢-indene) (Table
1, Entry 7)
White solid; mp 44–46 °C.
IR (KBr): 2929, 1729, 1602, 1466, 1430, 1313, 1269, 1226, 1133,
1076, 1035, 1016, 942, 872, 815, 759, 685, 641, 581, 485 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.15 (dd, J = 7.2, 15.6 Hz, 1 H),
3.40 (dd, J = 7.2, 15.6 Hz, 1 H), 4.21–4.34 (m, 4 H), 4.47 (t, J = 7.2
Hz, 1 H), 7.22–7.39 (m, 4 H).
chlorinating reagent, see: Schlama, T.; Gabriel, K.;
Gouverneur, V.; Mioskowski, C. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2342.
13C NMR (75 MHz, CDCl3): d = 38.83, 63.23, 66.08, 66.36, 114.24,
(3) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 4th ed.; Wiley-Interscience: New York,
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Adv. Synth. Catal. 2002, 344, 57. (c) Chan, T. H.; Brook, M.
A.; Chaly, T. Synthesis 1983, 203.
123.36, 124.81, 127.64, 130.18, 139.29, 139.42.
HRMS (APCI): m/z [M + H]+ calcd for C11H11ClO2: 211.0520;
found: 211.0517.
(4) Gallucci, R. R.; Going, R. J. Org. Chem. 1981, 46, 2532.
Synthesis 2009, No. 14, 2324–2328 © Thieme Stuttgart · New York

2328
J. Yu, C. Zhang
PAPER
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(13) One referee surmised that molecular chlorine might be the
active species in our system and advised us to check this
possibility by carrying out the reaction showed in Scheme 3
in the presence of 4 Å MS. Accordingly, 4¢-methylaceto-
phenone was treated with 1.1 equivalents of molecular
chlorine in ethylene glycol in the presence of 4 Å MS at
room temperature. After 20 hours, 48% of starting material
was recovered and only 7% of the desired cyclic ketal of
a-chloroketone was obtained, together with 2-methyl-2-p-
tolyl-1,3-dioxolane, which formed as the major product
(40%). Apparently, this result is distinct from that observed
with our PhICl2/ethylene glycol/4 Å MS system under which
the same cyclic ketal of a-chloroketone was obtained in 95%
yield within only 30 minutes (Table 1, entry 5). Therefore,
we believe that the mechanism shown in Scheme 1 is still
preferable.
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Synthesis 2009, No. 14, 2324–2328 © Thieme Stuttgart · New York