New, efficient synthesis of α-chloroketones using SiCl 4/urea-hydrogen peroxide or SiCl4/iodosylbenzene reagent systems

Article abstract of DOI:10.1080/00397911.2010.487173

Alkyl aryl ketones on treatment with SiCl₄/urea-hydrogen peroxide (UHP) or SiCl₄/iodosylbenzne reagent systems afforded -chloroketones in excllent yields, while ketones with higher enol content provide exclusively,-dichloroketones under exceedingly mild conditions. The reaction proceeds via the initial formation of silyl enol ethers. A polarized chlorine intermediate that resulted from the coordination of SiCl₄ with the in situ formed trichlorosilyl hypochlorite Cl₃SiOCl is thought to be the active chlorinating agent.

Full text of DOI:10.1080/00397911.2010.487173

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New, Efficient Synthesis of α-
Chloroketones Using SiCl4/
Urea–Hydrogen Peroxide or SiCl4/
Iodosylbenzene Reagent Systems
Abdel Aziz S. El-Ahl a , Akram H. Elbeheery b & Fathy A. Amer b
a Chemistry Department , Makkah University College, Umm Al-Qura
University , Makkah , Kingdom of Saudi Arabia
b Chemistry Department, Faculty of Science , Mansoura University ,
Mansoura , Egypt
Published online: 30 Mar 2011.
To cite this article: Abdel Aziz S. El-Ahl , Akram H. Elbeheery & Fathy A. Amer (2011) New, Efficient
Synthesis of α-Chloroketones Using SiCl4/Urea–Hydrogen Peroxide or SiCl4/Iodosylbenzene Reagent
Systems, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:10, 1508-1513, DOI: 10.1080/00397911.2010.487173
To link to this article: http://dx.doi.org/10.1080/00397911.2010.487173
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Synthetic Communications1, 41: 1508–1513, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.487173
NEW, EFFICIENT SYNTHESIS OF a-CHLOROKETONES
USING SiCl4/UREA–HYDROGEN PEROXIDE OR
SiCl4/IODOSYLBENZENE REAGENT SYSTEMS
Abdel Aziz S. El-Ahl,1 Akram H. Elbeheery,2 and
Fathy A. Amer2
1Chemistry Department, Makkah University College, Umm Al-Qura
University, Makkah, Kingdom of Saudi Arabia
2Chemistry Department, Faculty of Science, Mansoura University,
Mansoura, Egypt
GRAPHICAL ABSTRACT
Abstract Alkyl aryl ketones on treatment with SiCl4/urea–hydrogen peroxide (UHP) or
SiCl4/iodosylbenzne reagent systems afforded a-chloroketones in excllent yields, while
ketones with higher enol content provide exclusively a,a-dichloroketones under exceed-
ingly mild conditions. The reaction proceeds via the initial formation of silyl enol ethers.
A polarized chlorine intermediate that resulted from the coordination of SiCl4 with the in
situ formed trichlorosilyl hypochlorite Cl3SiOCl is thought to be the active chlorinating
agent.
Keywords a-Chloroketones; iodosylbenzene; silyl peroxides; tetrachlorosilane (TCS);
urea–hydrogen peroxide (UHP)
INTRODUCTION
a-Chloroketones are reactive and extremely useful intermediates that have
several applications in biological and organic synthesis, particularly for the synthesis
of natural products and heterocyclic compounds.[1] The increase of interest in the
chemistry of a-chloroketones arises from the observation that they are versatile
intermediates capable of mediating many different chemical transformations.[2]
Several useful reagents and procedures have been reported for the synthesis of
a-chloroketones. The direct conversion of ketones to a-chloroketones can be
induced using a variety of chlorinating agents such as N-chloro-succinimide,[3]
Received January 20, 2010.
Address correspondence to Abdel Aziz S. El-Ahl, Chemistry Department, Makkah University
College, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia. E-mail: elahl2002@yahoo.com
1508

EFFICIENT SYNTHESIS OF a-CHLOROKETONES
1509
tetraethylammonium trichloride,[4] trichloromethyl carbinols,[5] polymer-supported
chlorine,[6] and p-toluenesulfonyl chloride.[7] Selective a-chlorination of ketones at
the less substituted carbon has been reported via the initial formation of silyl enol
ethers as intermediates.[8] Copper(II) chloride has been used for the chlorination
of unsymmetrical ketones at the more substituted a-carbon atom.[9] The solvent-free
a-chlorination of ketones using [hydroxyl(tosyloxy)iodo]benzene (Koser’s reagent)
and MgCl2 under microwave irradiation has also been described.[10] Oxidative
a-chlorination of ketones using an aqueous H2O2=HCl chlorinating system has been
recently reported.[11] However, some of these methods suffer from drawbacks such
as long reaction times, use of hazardous chemicals, and cumbersome workup
procedures.
Although recent rapid advances in the methodology of a-chlorination of
ketones have been achieved, their preparation is frequently a troublesome operation,
and more efficient and flexible methods are still required.
In continuation of our interest in exploring new synthetic applications of novel
tetrachlorosilane (TCS) reagents,[12–14] we now report a new mild and inexpensive
method for the preparation of a-chloroketones via the reaction of ketones with
TCS in the presence of urea–hydrogen peroxide (UHP), a safe solid substituted with
liquid hydrogen peroxide) or iodocylbenzene.
RESULTS AND DISCUSSION
The reaction of 1-phenylethanone 1a with a mixture of 2 equivalents of TCS
and 1 equivalent of UHP[15] in methylene chloride at 0 ꢀC afforded 2-chloro-1-
phenylethanone, 2a, in 88% after usual aqueous workup followed by crystallization.
The reaction is very clean, with no side reactions. Indeed, the NMR of the crude
product does not show the presence of any impurity.
In an effort to generalize this chlorination methodology, several other
1-phenylethanone derivatives were subjected to the same conditions. The results
from these reactions are summarized in Table 1. The chlorination of 1-(4-tolyl)
ethanone 1b provided 2-chloro-1-(4-tolyl) ethanone 2b in 92% yield. Interestingly,
Table 1. Reaction of ketones with TCS=UHP or TCS=PhIO reagent systems
Compound
R1
R2
Time (h)a(b)
Yield (%)a(b)
Mp (ꢀC) (lit. mp)
2a
2b
2c
2d
2e
2f
C6H5-
H
1.2 (4.5)
1.0 (4)
1.0 (4)
1.0 (4)
1.0 (4)
1.5 (5.5)
1.5 (6)
1.5 (6)
1.5 (5.5)
88 (72)
92 (75)
93 (76)
92 (75)
93 (77)
85 (70)
87 (73)
85 (71)
76 (66)
55 (54–55)[11]
57 (56.5–57.5)[17a]
98 (98–99)[17b]
116 (117–118)[17c]
101 (101–102)[17d]
96–98 (103)[17e]
77 (77–79)[17f]
58–60 (61–62)[17g]
Oil
4-CH3C6H4-
4-CH3OC6H4-
4-BrC6H4-
4-ClC6H4-
3-NO2C6H4-
2-Naphthyl
C6H5-
H
H
H
H
H
2g
2h
2i
H
C6H5-
-COCH3
CH3-
aYields and reaction time using TCS=UHP.
bYields and reaction time using TCS=PhIO.

1510
A. A. S. EL-AHL, A. H. ELBEHEERY, AND F. A. AMER
the ring methyl group was not chlorinated under this condition, thus excluding the
radical mechanism. 1-(4-Methoxyphenyl)ethanone 1c, which carries a strong elec-
tron-releasing group on the ring, was readily converted into 2-chloro-1-(4-methoxy-
phenyl)ethanone 2c in 93%. It is concluded from these results that electron-rich
aryl groups activate the ketones in this chemoselective electrophilic oxidative chlori-
nation reaction at the a-carbon without further electrophilic chlorination at the
aromatic nucleus. Although electron-poor groups slightly increased the reaction time
for the starting material to be consumed, no pronounced effect on the yield of reac-
tion was observed. This was demonstrated from chlorination of 1-(4-bromophenyl)
ethanone 1d, 1-(4-chlorophenyl) ethanone 1e, and 1-(3-nitrophenyl) ethanone 1f,
which afforded the corresponding a-chloroketones in 92%, 93%, and 85% yield
respectively.
Ketones with more enol content, such as 1-(2-naphthyl) ethanone 1g,
1,2-diphenyl-ethanone 1h, and 2,4-pentanedione 1i, afforded exclusively the
a,a-dichlorinated products in good yields. This presumably may be attributed to
the more facile formation of silyl enol ethers from these ketones and their mono-
chlorinated products.
The reaction between TCS and UHP adduct leading to the effective chlorinat-
ing agent of ketones is not clear yet. The first step of the reaction could be the for-
mation of bis(trichlorosilyl)peroxide intermediate (A).[16] Further reaction of A with
Scheme 1. Oxidative a-chlorination of ketones using TCS-UHP reagent system.

EFFICIENT SYNTHESIS OF a-CHLOROKETONES
1511
liberated hydrogen chloride produces the trichlorsilyl hypochlorite (B). The coordi-
nation of B with TCS produces the ionized chlorine intermediate (C). Electrophilic
attack of C on the in situ formed silyl enol ethers (D) finally furnishes the corre-
sponding a-chloroketones (Scheme 1).
To get more information about the sequence of this reaction, we conducted the
reaction of ketones with TCS, using iodosylbenzene as an oxidizing agent substitute
of UHP. Under this condition, the ketones 1a–i afforded the same products as in the
case of TCS=UHP reagent, but the yields were lower and the reaction time was
longer (Table 1). A trichlorosilyl hypochlorite intermediate is also thought to be
formed in this reaction [Eq. (2)] subsequently; the reaction proceeded in the same
manner shown in Scheme 1. The structures of a-chloroketones have been confirmed
using elemental and spectroscopic analyses (cf. Table 2).
Table 2. Analytical and spectral data of a-chloroketones 2a–2i
Analysis (%) calcd.
(found)
Spectral data: 1H NMR [CDCl3=
Mol.
formula (Mr)
TMS, d ppm, J (Hz)], IR
(KBr, cmꢁ1); mass (m=z)
Compound
C
H
2a
C8H7ClO
(154.59)
62.15
(62.29)
4.56
(4.41)
IR: 3061, 2951, 1695, 1596, 1449, 1000, 748. MS:
m=z (%): 154 (Mþ, 10), 105 (100), 77 (88).
1H NMR: d ¼ 7.93–7.44 (m, 5H), 4.7 (s, 2H).
IR: 3057, 2960, 1698, 1592, 1449, 984, 756. 1H
NMR: d ¼ 7.46 (d, 2H, J ¼ 7.5 Hz), 7.01 (d, 2H,
J ¼ 7.5 Hz), 4.63 (s, 2H), 2.35 (s, 3H).
2b
2c
2d
2e
C9H9ClO
(168.62)
64.11
(63.98)
5.38
(5.13)
C9H9ClO2
(184.62)
58.55
(58.43)
4.91
(4.82)
IR: 3065, 2955, 1700, 1593, 988, 756. 1H NMR:
d ¼ 7.85 (d, 2H, J ¼ 7.5 Hz), 7.43 (d, 2H,
J ¼ 7.5 Hz), 4.68 (s, 2H), 3.93 (s, 3H).
C8H6BrClO
(233.49)
41.15
(41.23)
2.59
(2.68)
IR: 2998, 2952, 1695, 1584, 1449, 1006, 695.
1H NMR: d ¼ 7.83 (d, 2H, J ¼ 7.5 Hz), 7.63 (d,
2H, J ¼ 7.5 Hz), 4.61 (s, 2H).
C8H6Cl2O
(189.04)
50.83
(50.66)
3.20
(3.37)
IR: 2998, 2952, 1694, 1590, 1449, 999, 782. MS:
m=z (%): 188 (Mþ, 3.4), 139 (100), 111 (43.6).
1H NMR: d ¼ 7.88 (d, 2H, J ¼ 7.5 Hz), 7.45 (d,
2H, J ¼ 7.5 Hz), 4.65 (s, 2H).
2f
C8H6ClNO3
(199.59)
48.14
(47.93)
3.03
(3.25)
IR: 2998, 3089, 1691, 1614, 1526, 1349, 1110, 819,
741, 675. 1H NMR: d ¼ 8.77 (s, 1H), 8.6 (d,
1H, J ¼ 7.6), 8.3 (d, 1H, J ¼ 7.6), 7.68 (m, 1H),
4.71 (s, 2H).
2g
C12H8Cl2O
(239.10)
60.28
(60.43)
3.37
(3.29)
IR: 3057, 2944, 1701, 1621, 1591, 1464, 924, 740.
MS: m=z (%): 238 (Mþ, 7.3), 204 (3.4), 155
(100), 127 (68.4). 1H NMR: d ¼ 8.63 (s, 1H),
8.12–7.58 (m, 6H), 6.84 (s, 1H).
2h
2i
C
14H10Cl2O
(265.13)
63.42
(63.35)
3.80
(3.56)
IR: 3070, 3031, 2951, 1694, 1595, 995, 758. MS:
m=z (%): 230 (Mþ-Cl, 1.0), 229 (4), 105 (100),
77 (43.6). 1H NMR: d ¼ 8.15–7.29 (m, 10H).
IR: 3020, 2951, 1716, 1617, 1397, 1267, 1035, 912.
1H NMR: d ¼ 2.28 (s, 6H). 13C NMR:
d ¼ 23.86, 108.08, 188.91.

1512
A. A. S. EL-AHL, A. H. ELBEHEERY, AND F. A. AMER
CONCLUSION
In conclusion, we have presented a very cheap, chemoselective, fast, safe, and
ecofriendly procedure for chlorniation of ketones at the a-carbon without any trace
of nuclear chlorination at the aromatic ring. Using TCS as chlorine source in the
presence of easily prepared and easily handled oxidizing agents available in large
amounts such as UHP or iodosylbenzene offers useful new chlorinating agents,
which can be used for chlorination of different organic compounds as alternative
for the existing methods.
EXPERIMENTAL
Melting points were determined in open capillary tubes and are uncorrected.
Infrared (IR) spectra were recorded on Thermo Nicolet nexus 470 Fourier transform
(FT)–IR and Mattson 5000 FT-IR spectrophotometer with only selected absorptions
being recorded. Absorption maxima were recorded in centimetersꢁ1. Nuclear
magnetic resonance (NMR) spectra were run on a 1H NMR Varian-Mercury
(200-MHz) FT-NMR spectrometer. Spectra were measured using CDCl3 as solvent
with chemical shifts quoted in parts per million (d ppm) using tetramethylsilane
(TMS) as internal standard. The mass spectra (MS) were recorded on a GC-MS
QP-1000 EX Schmiadzu (Japan) mass spectrometer. Elemental analyses were carried
out at the Microanalytical Unit, Faculty of Science, Cairo University.
General Procedure
In a typical procedure, TCS (1.2 ml, 10 mmol) was added to a mixture of
ketone (5 mmol) and UHP (0.47 g, 5 mmol) or iodosylbenzene (1.05 g, 5 mmol) in
anhydrous methylene chloride (15 ml). This mixture was stirred with exclusion of
moisture at 0 ꢀC until the ketone was consumed (monitoring by thin-layer chroma-
tography). The mixture was then poured into ice-cooled water (50 ml) and extracted
with chloroform (2 ꢂ 50 ml). The extracts were dried over anhydrous sodium sulfate
and evaporated under reduced pressure. The residue was purified by crystallization
from diethyl ether to give pure products (cf. Table 1).
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