Silicon mediated synthesis and selected transformations of β-chloroketones

Article abstract of DOI:10.1016/j.cclet.2011.05.007

A combination of tetrachlorosilane (TCS) and phenol in dichloromethane was found to be an efficient reagent for hydrochlorination of α,β- unsaturated ketones to afford the corresponding β-chloroketones in good yield at ambient temperature. Reactions of th

Full text of DOI:10.1016/j.cclet.2011.05.007

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1171–1174
www.elsevier.com/locate/cclet
Silicon mediated synthesis and selected
transformations of b-chloroketones
a
Tarek A. Salama a,b, , Saad S. Elmorsy
*
a Chemistry Department, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt
b Chemistry Department, Faculty of Education, Amran University, Amran, Yemen
Received 16 February 2011
Available online 18 July 2011
Abstract
A combination of tetrachlorosilane (TCS) and phenol in dichloromethane was found to be an efficient reagent for hydro-
chlorination of a,b-unsaturated ketones to afford the corresponding b-chloroketones in good yield at ambient temperature.
Reactions of the titled compounds with TCS-NaN3 as well as with nitriles utilizing TCS-ZnCl2 to give 1,5-disubstituted tetrazole
derivatives or b-amido ketones respectively are also described.
# 2011 Tarek A. Salama. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Tetrachlorosilane; Phenol; b-Chloroketones; Synthesis; Tetrazoles; b-Amido ketones
b-Haloketones are useful intermediates in organic synthesis as they undergo a number of substitution reactions at
halogen, as well as protonation and addition reactions at the carbonyl group [1]. However, whereas the methods of
synthesis of a-haloketones are numerous, it is apparently more difficult to obtain b-halo derivatives which suffer
spontaneous dehydrohalogenation if the conditions are too drastic. Olefin acylation [2] and addition of hydrogen
halides to a,b-unsaturated ketones [3] are mainly the most applicable procedures for the synthesis of b-haloketones.
The latter reaction often leads to salts by protonation of the carbonyl oxygen, which then renders the carbon–carbon
double bond unreactive toward hydrogen halide addition. The reaction of an enone with a tetraalkylammonium halide
in trifluoroacetic acid is a convenient synthesis for b-iodo ketones but remains less efficient for b-chloroketones [4].
Oxidation of iodide or bromide ions by ceric ammonium nitrate in the presence of cyclopropyl alcohols provides a
route to b-iodo/bromoketones but not for b-chloroketones [5]. Halosilanes have been used in the preparation of b-
haloketones. For example, iodotrimethylsilane adds to a,b-unsaturated carbonyl compounds to give b-iodo carbonyl
derivatives [6] or their acetals [7], in the presence of diols. b-Haloketones were also prepared through the halogenation
of b-siloxyketones with a halosilane under BiCl3–ZnI2 catalysis [8]. On the other hand, combinations of Me3SiCl or
SiCl4 and phenol have been used for t-butoxycarbonyl group (Boc) deprotection in solid phase peptide synthesis [9]. In
conjunction with our interest in exploring the utility of in situ reagents based on tetrachlorosilane (TCS) [10] in organic
synthesis, we report herein a facile and mild procedure for the hydrochlorination of a,b-unsaturated ketones to give the
corresponding b-chloroketones in good yields utilizing the inexpensive and readily available tetrachlorosilane–phenol
* Corresponding author at: Chemistry Department, Faculty of Education, Amran University, Amran, Yemen.
E-mail address: tasalama@yahoo.com (T.A. Salama).
1001-8417/$ – see front matter # 2011 Tarek A. Salama. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.05.007

1172
T.A. Salama, S.S. Elmorsy / Chinese Chemical Letters 22 (2011) 1171–1174
Cl
O
1. SiCl , PhOH
O
4
CH Cl , r.t.
2
2
Ar
Ar'
Ar
Ar'
2. H O
2
1a-f
2a-f
1a, 2a; Ar = Ar' = Ph
1b, 2b; Ar = Ph, Ar' = 4-ClC H -
6
4
1c, 2c; Ar = Ph, Ar' = 3-ClC H -
6
4
1d, 2d; Ar = 4-MeOC H -, Ar' = Ph
6
4
1e, 2e; Ar = 4-MeC H -, Ar' = 4-ClC H -
6
4
6 4
6 4
1f, 2f; Ar = 4-MeOC H -, Ar' = 4-ClC H -
6
4
Scheme 1.
system [9c]. Transformations of the prepared b-chloroketones into 1,5-disubstituted tetrazoles or b-amido ketones
were also accomplished through their reactions with SiCl4–NaN3 [10e] or with nitriles in the presence of SiCl4–ZnCl2
[10b] respectively. The reaction of a,b-unsaturated ketones with SiCl4-PhOH works well giving good yields of
respective b-chloroketones after aqueous work up (Scheme 1, Table 1). The structure of isolated b-chloroketones was
assigned based on their spectral analyses as well as by matching their melting points with reported analogues [3b,11].
The generality of the process was examined through applying the reaction to various examples of a,b-unsaturated
ketones, however, unfortunately, the reaction failed with arylidenes of alicyclic ketones as well as with aliphatic
unsaturated ketones. For example, 2,6-dibenzylidenecyclohexanone was recovered without reaction (entry 7, Table 1)
and 4-methylpent-3-en-2-one gave a complex mixture with no preparative value (entry 8, Table 1).
The mechanism of synthesis of b-chloroketones 2 has not been exactly determined. It is noteworthy to mention that
no reaction was observed in the absence of either the PhOH or SiCl4. However, a plausible pathway for the present
reaction may proceed as depicted in Scheme 2 through 1,4-addition of stoichiometric reagent generated in situ from
the reaction of TCS and phenol in 1:2 molar ratio (proposed hexacoordinate silicon complex A) to a,b-unsaturated
ketones. Formation of A may find a support from the reported reaction of chlorotrimethylsilane (TMSCl) with phenol
in which a pentacoordinate silicon complex (via an equimolar reaction of TMSCl and phenol) was proposed [9b].
However, we presume that formation of a hexacordinate silicon complex is more probable [12]. In addition, 1,4-
addition of halosilanes to enones is well-documented [6,7].
Table 1
Reaction of a,b-unsaturated ketones with TCS-PhOH reagent.
Entry
Substrate
Time (h)
Product
Yield (%)a
1
2
3
4
5
6
7
8
1,3-Diphenylpropenone
11
16
15
14
16
17
24
24
2a
2b
2c
2d
2e
2f
–
82
74
65
67
71
61
–
3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one
3-(3-Chlorophenyl)-1-phenylprop-2-en-1-one
1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-one
3-(4-Chlorophenyl)-1-p-tolylprop-2-en-1-one
3-(3-Chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one
2,6-Dibenzylidenecyclohexanone
4-Methylpent-3-en-2-one
–
–
a
Isolated yield.
OH
O
Ph
Cl
Cl
Ph
Ph
Cl
Cl
H
Ph
Cl
Cl
H
H
H+Cl-
Ar'
O
Si
O
Ar
O
Si
O
Ar
O
Si
O
Cl
O
H
Cl
O
Ph
Ar
Ar'
Cl
Cl
Ph
DCM
+
SiCl4
Ar'
Cl
- 2 PhOH
- SiO2
H2O
A
O
Cl
OH Cl
Ar
Ar'
Ar
Ar'
2
Scheme 2.

T.A. Salama, S.S. Elmorsy / Chinese Chemical Letters 22 (2011) 1171–1174
1173
O
O
HN
R
O
Cl
TCS-NaN
TCS, ZnCl
N
N
3
2
Ar'
N
Ar
Ar'
MeCN, r.t.
Ar
Ar'
RCN, DCM, r.t.
N
Ar
2a, 3a; Ar = Ar' = Ph; Yield 94%
2b, 3b; Ar = Ph, Ar' = 4-Cl C H -; Yield 89%
4a; Ar = Ar' = Ph, R = Me; Yield 83%
4b; Ar = Ph, Ar' = 4-Cl C H -, R = Ph; Yield 74%
6
4
6
4
Scheme 3.
To explore the synthetic utility of b-chloroketones, we pursued study of their reactions with some nucleophiles to
obtain the respective b-functionalized ketones. Thus, reaction of b-chloroketones with TCS/NaN3 as well as with
nitriles in the presence of TCS/ZnCl2 was examined (Scheme 3). While the later led to smooth formation of the
expected b-amido ketones 4 presumably via a Ritter type reaction [13], the earlier, did not give the expected b-azido
ketones but gave rather the 1,5-disubstituted tetrazoles 3 through an addition process at the carbonyl group [10e,14].
In conclusion, a new approach to b-chloroketones has been presented. Considering the mild conditions of the
protocol, cheap and ease of reagent handling, and extensive use of b-chloroketones in synthesis of b-amido ketones as
well as 1,5-disubstituted tetrazole derivatives, the present method provides an alternative pathway to important
starting materials and intermediates in organic synthesis. Furthermore, the in situ reagents described in this work, may
find additional applications expanding the synthetic value of tetrachlorosilane in synthetic organic chemistry.
1. Experimental
1.1. Typical procedure for the synthesis of b-chloroketones
To a mixture of a,b-unsaturated ketone (5 mmol) and phenol (10 mmol) in CH2Cl2 (20 mL), SiCl4 (10 mmol) was
added and the reaction mixture was stirred at room temperature. On completion (the reaction was monitored by TLC),
the mixture was quenched with cold water, extracted with CHCl3, dried over anhydrous MgSO4 and the solvent was
vaporized under vacuum and the residue was chromatographed using the eluent system pet. ether–ethyl acetate (20:1)
to give pure 2c–f or treated with ethanol (5 mL) to give pure 2a,b.
Data for 2e as a representative example are showed: 3-Chloro-3-(4-chlorophenyl)-1-p-tolylpropan-1-one 2e. Yield
71%; purification by column chromatography using pet. ether–ethyl acetate (20:1) as eluent system; Mp 87 8C; IR
(KBr, cmÀ1): n 3094, 3027, 2920, 1679 (COCH2), 1599 (C C), 1515, 1451, 1413, 1357, 1329, 1237, 1063, 856, 753,
726, 699; 1H NMR (CDCl3): d 7.84 (d, 2H, J = 7.8 Hz, Ar-H), 7.42 (d, 2H, J = 7.4 Hz, Ar-H), 7.34–7.22 (m, 4H, Ar-
H), 5.57 (t, 1H, J = 6.2 Hz), 3.88 (ABd, 1H, J = 16.5 Hz), 3.59 (ABd, 1H, J = 16.5 Hz), 2.41 (s, 3H); EI-MS (m/z, %):
256 (M+–HCl, 81), 241 (33), 221 (35), 178 (31), 165 (32), 119 (84), 91 (100); Anal. Calcd. for C16H14Cl2O (293.19):
C, 65.53; H, 4.78. Found: C, 65.32; H, 4.68.
1.2. Synthesis of 1,5-disubstituted tetrazoles
A typical procedure for the reaction of 2 with SiCl4/NaN3 in the ratio 1:2:6 to give 3: To a stirring mixture of 2 and
NaN3 in CH3CN at room temperature was added SiCl4 and the mixture left to stir until TLC showed disappearance of
the starting material. The reaction was then poured into aq. NaHCO3 solution and the mixture was extracted with
CH3COOEt. The extracts were dried over MgSO4 and concentrated, cooled to give pure 3.
1.3. Synthesis of b-amidoketones
A typical procedure for the reaction of 2 with nitriles and SiCl4/ZnCl2 in the ratio 1:2:2:2 to give 4: To a stirring
mixture of 2, ZnCl2 and nitrile, in CH2Cl2 at room temperature was added SiCl4 and the mixture left to stir until TLC
showed disappearance of the starting material. The reaction was then poured into aq. NaHCO3 solution and the
mixture was extracted with CH2Cl2. The extracts were dried over MgSO4, evaporated and the residue was purified by
silica gel column chromatography (pet. ether–ethyl acetate 10:1) to give pure 4.

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T.A. Salama, S.S. Elmorsy / Chinese Chemical Letters 22 (2011) 1171–1174
Acknowledgment
We are indebted to Prof. Mohamed. A. Ismail for generous spectroscopic assistance.
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