An efficient fluorination of β-ketosulfones promoted by a room-temperature ionic liquid at ambient conditions under ultrasound irradiation using Selectfluor F-TEDA-BF4

Article abstract of DOI:10.1016/j.cclet.2010.06.030

The fluorination reaction involving a β-ketosulfones by Selectfluor was efficiently promoted by the ionic liquid, [Hbim]BF₄ (IL) as a reaction medium with methanol as co-solvent at room temperature under ultrasonic irradiation to afford the corresponding mono and difluoro-β-ketosulfones in excellent yields. The advantages of this method include among others the use of a recyclable, non-volatile ionic liquid, which promotes this protocol under room temperature without the requirement of any added catalyst under ultrasonic irradiation.

Full text of DOI:10.1016/j.cclet.2010.06.030

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 1399–1402
www.elsevier.com/locate/cclet
An efficient fluorination of b-ketosulfones promoted by a
room-temperature ionic liquid at ambient conditions under
ultrasound irradiation using SelectfluorTM F-TEDA-BF4
Mohammad Reza Poor Heravi
Department of Chemistry, Payame Noor University (Pnu), P. O. Box. 97, Abhar, Zanjan, Iran
Received 24 March 2010
Abstract
The fluorination reaction involving a b-ketosulfones by SelectfluorTM was efficiently promoted by the ionic liquid, [Hbim]BF4
(IL) as a reaction medium with methanol as co-solvent at room temperature under ultrasonic irradiation to afford the corresponding
mono and difluoro-b-ketosulfones in excellent yields. The advantages of this method include among others the use of a recyclable,
non-volatile ionic liquid, which promotes this protocol under room temperature without the requirement of any added catalyst under
ultrasonic irradiation.
# 2010 Mohammad Reza Poor Heravi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Fluorination; Ultrasound irradiation; b-Ketosulfones; SelectfluorTM; Ionic liquids (ILs)
Fluorine-containing organic compounds play an important role in material science as well as pharmaceutical and
agrochemical chemistry [1]. As a consequence fluorinated building blocks are required. Several methods are available
to introduce a difluoromethyl group into organic substrates. For example, reactions of fluorinated nucleophiles
including (difluoromethyl)-dimethylphenylsilane [2] (chlorodifluoromethyl)trimethylsilane, or difluoromethylphe-
nylsulfone [3], have been reported. As an alternative, modification of the existing framework by deoxofluorination of
aldehydes, either directly using a variety of electrophilic reagents (SeF4, DAST or SF4) [4], or indirectly by
fluorination of 1,2- or 1,3-dithianes using BrF3 and other in situ-generated halogen fluorides, is possible [5,6]. The use
of ultrasound in organic transformation is now well known to enhanced reaction rates and yields/selectivity of
reactions [7], and in several cases facilities organic transformation at ambient conditions which otherwise require
drastic conditions of temperature and pressure [8], In recent years, studies of low waste routes and reusable reaction
media for enhanced selectivity and energy minimization are the key interests of synthetic organic chemists’ world over
[9]. In this context, in recent times, the use of room-temperature ionic liquids (RTILs) as ‘‘green’’ solvents in organic
synthetic processes has gained considerable importance due to their solvating ability, negligible vapor pressure, and
easy recylability [10].
E-mail address: heravimr@yahoo.com.
1001-8417/$ – see front matter # 2010 Mohammad Reza Poor Heravi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.06.030

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M.R.P. Heravi / Chinese Chemical Letters 21 (2010) 1399–1402
1. Experimental
A mixtures containing of 2-(4-bromophenylsulfonyl)-1-phenylethanone (339 mg, 1 mmol), 2 mL of [Hbim]BF4
(IL) to which 0.5 mL of methanol was added as a co-solvent and SelectfluorTM (715 mg, 2.1 mmol) was then added
and sonicated in an atmosphere of argon at ambient conditions in a thermostated (25 Æ 1 8C) ultrasonic cleaning bath
for 20 min. After completion of the reaction (as indicated by TLC), the reaction mixture was quenched by the addition
of crushed ice (50 g) and stirred for about 1 h, and extracted under reduced pressure and purified by flash silica gel
chromatography [petroleum ether/EtOH (95:5)] to afford the mono and difluoro-b-ketosulfones 2b (2%), 3b (88%).
2-(4-Bromophenylsulfonyl)-2-fluoro-1-phenylethanone (2b): Yield (2%); (KBr, cmÀ1): nmax 3093, 2982, 1721
(C O), 1558, 1441, 1366, 1236, 919, 855 and 822; 1H NMR (500 MHz, CDCl3): d 6.43 (d, 1H, J = 48.1 Hz), 7.43 (t,
2H, J = 7.6), 7.67 (ddd, 1H, J = 8.5, 2.5 and 1.5 Hz), 7.79–7.91 (m, 2H), 7.94 (m, 2H, J = 8.5 Hz) and 8.11 (dd, 2H,
J = 8.5 and 1.5 Hz); 13C NMR (126 MHz, CDCl3): d 111.1 (d, J = 250.2 Hz), 115.9, 128.7, 131.5, 132.7, 133.7, 136.0,
141.0, 146.7 and 195.5 (C O); 19F NMR (235 MHz, CDCl3): d À182.3 (d, J = 48.1 Hz, 1F); (EI) Found: M+,
355.9505, C14H10BrFO3S requires M+, 355.9602; LRMS m/z (EI): 357 (M+, 100%), 293 (M–SO2, 6%), Elemental
analysis: Found (%): C, 47.12; H, 2.96; S, 8.99. Calcd. for C14H10BrFO3S: C, 47.08; H, 2.82; S, 8.98.
2-(4-Bromophenylsulfonyl)-2,2-difluoro-1-phenylethanon (3b): Recrystallized from ethanol (88%); mp 66 8C; IR
(KBr, cmÀ1): nmax 3093, 1726 (C O), 1553, 1437, 1366, 1246, 925, 866 and 824; 1H NMR (500 MHz, CDCl3): d 7.58
(t, 2H, J = 7.7), 7.79 (ddd, 1H, J = 8.6, 2.3 and 1.3 Hz), 7.88–7.93 (m, 2H), 7.98 (m, 2H, J = 8.6 Hz) and 8.04 (dd, 2H,
J = 8.6 and 1.3 Hz); 13C NMR (126 MHz, CDCl3): d 87.5, 116.2 (t, CF2, J = 301.8 Hz), 128.9, 130.6, 130.7, 131.5,
132.0, 133.0, 135.5 and 184.0 (C O); 19F NMR (235 MHz, CDCl3): d À102.7 (s, CF2, 2F); (EI) Found: M+, 373.9445,
C14H9BrF2O3S requires M+, 373.9089; LRMS m/z (EI): 376 (M+, 100%), 311 (M–SO2, 6%), Elemental analysis:
Found (%): C, 44.78; H, 2.35; S, 8.70. Calcd. for C14H9BrF2O3S: C, 44.82; H, 2.42; S, 8.55.
2,2-Difluoro-2-(2-nitrophenylsulfonyl)-1-phenylethanone (3e): Recrystallized from ethanol (92%); mp 59 8C; IR
(KBr, cmÀ1): nmax 3098, 1735 (C O), 1567, 1488, 1388, 1255, 945, 888 and 854; 1H NMR (500 MHz, CDCl3): d 3.78
(s, 3H), 6.89 (d, 2H, J = 8.5), 7.35 (d, 1H, J = 8.5 Hz), 7.45 (t, 2H, J = 7.7 Hz), 7.65 (t, 2H, J = 7.4 Hz) and 7.90 (d, 2H,
J = 7.4 Hz); 13C NMR (126 MHz, CDCl3): d 55.5, 114.3 (t, CF2, J = 301.8 Hz), 115.1, 127.8, 128.1, 132.1, 134.1,
136.3, 137.8, 145.1 and 196.4 (C O); 19F NMR (235 MHz, CDCl3): d À102.9 (s, CF2, 2F); (EI) Found: M+, 341.0201,
C14H9F2NO5S requires M+, 341.0212; LRMS m/z (EI): 341 (M+, 3%), 277 (M-SO2, 5%). Elemental analysis: Found
(%): C, 49.33; H, 2.59; S, 9.45. Calcd. for C14H9F2NO5S: C, 49.27; H, 2.66; S, 9.40.
2. Results and discussion
Our previous research on fluorination of a-hydrogen activated compounds [11], a series of b-ketosulfones 1a–k
were prepared by reaction of arylthiols with a-bromoacetophenone in the presence of sodium carbonate using
literature methods then oxidation with m-CPBA [12]. The ionic liquid, [Hbim]BF4 (IL), was synthesized by the
method reported [13]. We thought that there is scope for further innovation towards milder reaction conditions, short
reaction time and better yields in the synthesis of mono and difluoro-b-ketosulfones, which was achieved by using
‘green’ imidazolium ionic liquid, [Hbim]BF4 (IL) as reaction media as well as promoter in the absence of any added
catalyst under ultrasound irradiation at ambient conditions (Scheme 1).
We compared our results for synthesis of mono and difluoro-b-ketosulfones with the reaction rates for the sodium
carbonate as base in acetonitrile (dry) (entry 1), in methanol (dry) (entry 2), sodium carbonate as base in methanol
(dry) (entry 3), with [Hbim]BF4 (IL) without co-solvent (entry 4), [Hbim]BF4 (IL) with MeOH as co-solvent (entry 5)
under thermal conditions. The results are recorded in Table 1. The fluorination of b-ketosulfone (e.g. 1b) in [Hbim]BF4
(IL) with MeOH as co-solvent by SelectfluorTM as fluorinating reagent under ultrasound irradiation 50 kHz is
investigated and maximum yield of 3b (88%) at room temperature in 20 min is obtained.
The sonochemical synthesis of difluoro-b-ketosulfone 2b using IL containing 25 vol.% of MeOH was observed to
be the most optimum condition for the synthesis of 2b in maximum yields at ambient temperature in the absence of any
added catalyst. Hence, all further reactions with other b-ketosulfones were carried out under these conditions. The
experimental procedure for this reaction is remarkably simple and requires no toxic organic solvents. The reactions
were carried out at room temperature for 15–100 min by taking a 1:2.1 mol ratio. The IL acts as Brønsted acid catalyst
as well as solvent at ambient temperature (25 8C) under ultrasonic (Scheme 1). The MeOH was added as co-solvent to
solubilise. The results are summarized in Table 2. b-Ketosulfones 1a–j (entries 1–10) afforded the desired products

[(Scheme_1)TD$FIG]
M.R.P. Heravi / Chinese Chemical Letters 21 (2010) 1399–1402
1401
Scheme 1.
Table 1
The synthesis of 2b, 3b under various reaction conditions by SelectfluorTM
.
Entry
Solvent/co-solvent
Reaction conditions
Yield 2b (%)a
Yield 3b (%)a
b
1
2
Acetonitrile (dry), N2/Na2CO3
Methanol (dry)
RT, stirring, over night
RT, stirring, over nigh
RT, stirring, over nigh
RT, stirring, over night
RT, stirring, over night
RT, 80 min
11
2
3
8
5
2
2
3
5
5
4
48
4
3
Methanol (dry), N2/Na2CO3
33
50
52
58
88
70
50
62
55
4
2 mL of [Hbim]BF4 + no co-solvent
2 mL of [Hbim]BF4 + 0.5 mL MeOH
2 mL of [Hbim]BF4 + no co-solvent
2 mL of [Hbim]BF4 + 0.5 mL MeOH
2 mL of [Hbim]BF4 + 0.5 mL EtOH
2 mL of [Hbim]PF6 + no co-solvent
2 mL of [Hbim]PF6 + 0.5 mL MeOH
2 mL of [Hbim]PF6 + 0.5 mL EtOH
5
6
7
RT, 20 min
8
RT, 50 min
7
RT, 80 min
10
11
RT, 30 min
RT, 75 min
a
Isolated yields.
b
Data taken from Ref. [11].
3k–l in good yields. The reaction of aliphatic b-ketosulfones 1k–l (entries 11, 12) did not occur. The pKa value of the
IL [Hbim]BF4 is 0.5 that it by virtue of its inherent Brønsted acidity conferred by the most acidic NH hydrogen and
maximum polarity. It was assumed that the nature of the anion would govern the electrophilicity of the imidazolium
cation, which in turn has a bearing on the acidity of IL. It was observed that with increasing basicity of the anion
Table 2
The synthesis of mono and difluoro-b-ketosulfones 2, 3(a–k) under sonochemical condition [Hbim]BF4/MeOH by SelectfluorTM
.
Entry
R1
R2
Time (min)
Monofluoro product 2
Yield (%)a
Difluoro product 3
Yield (%)a,b
1
2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
CH3
50
20
2a
2b
2c
2d
2e
2f
5
3a
3b
3c
3d
3e
3f
65
4-BrC6H4
4-CH3C6H4
4-CH3OC6H4
2-NO2C6H4
2-Naphthyl
C6H5CH2
4-CH3OC6H4
C6H5
2
88
3
30
3
85
4
30
3
90
5
20
3
92
6
15
5
95
7
15
2g
2h
2i
2
3g
3h
3i
96
8
15
2
98
9
60
3
50
10
11
12
2-Methylenefuran
c-C6H11
C6H5
C6H5
C6H5
100
>100
>100
2j
0
3j
40
2k
2l
N.R.c
N.R.c
3k
3l
N.R.c
N.R.c
n-C6H13
a
Isolated yields.
Products are characterized by melting point, 1H NMR, 13C NMR and HRMS.
b
c
No reaction.

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M.R.P. Heravi / Chinese Chemical Letters 21 (2010) 1399–1402
Table 3
13C NMR chemical shifts and IR data for the carbonyl group 2b.
Entry
1
Substrate
Chemical shifts (ppm)
187.9
IR, n (cmÀ1 a
)
1702
[DT$INLE]
2
192.3
1688
[DT$INLE]
a
Recorded with neat sample.
(increasing pKa of the corresponding acid), there was a progressive increase in yield [14]. I believed that the
enolization of b-ketosulfones 1a–j in [Hbim]BF4 (IL) took place faster than aliphatic b-ketosulfones 1k–l (entries 11,
12); therefore fluorination reaction by SelectfluorTM led to products 3k–l. It is presumed that the efficiency using
ultrasound irradiation is due to the cavitations phenomena, the energy being more efficiently transmitted to the
substrates compared to the reactions performed under silent condition at room temperature. On the word, the
cavitations mediated by ultrasonic irradiation can cause extension of the surface area available for reaction.
The Brønsted acidity is conferred by the –NH proton of [Hbim]BF4 (IL) (chemical shift of 14.59 ppm) capable of
bonding with the carbonyl oxygen of the b-ketosulfones.
Evidence for this was obtained by recording the 13C NMR spectra of 2-(4-bromophenylsulfonyl)-1-phenylethanone
1b with an external lock of D2O and with one equivalent of the IL under similar conditions. The results are recorded in
Table 3.
A significant shift of ꢀ4 ppm for the carbonyl carbon of the b-ketosulfone 1b by the interaction with the IL was
observed. Additional evidence was obtained by recording their IR spectra neat wherein also a significant shift to a
lower wave number by 6–14 cmÀ1 was observed.
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