Fluorination of activated aromatic systems with Selectfluor F-TEDA-BF4 in ionic liquids

Article abstract of DOI:10.1016/j.jfluchem.2007.11.006

Selectfluor was shown to be soluble in ionic liquid, thus allowing the 'green' electrophilic fluorination of activated aromatic systems compounds in high chemoselectivity and yields.

Full text of DOI:10.1016/j.jfluchem.2007.11.006

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 217–221
www.elsevier.com/locate/fluor
Fluorination of activated aromatic systems with
SelectfluorTM F-TEDA-BF4 in ionic liquids
*
Mohammad Reza Poor Heravi
Chemistry Department, Payame Noor University, P.O. Box 97, Ahar, Iran
Received 21 October 2007; received in revised form 8 November 2007; accepted 14 November 2007
Available online 22 November 2007
Abstract
SelectfluorTM was shown to be soluble in ionic liquid, thus allowing the ‘green’ electrophilic fluorination of activated aromatic systems
compounds in high chemoselectivity and yields.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Fluorination; Ionic liquids; Activated aromatic systems; SelectfluorTM
1. Introduction
2. Results and discussion
The replacement of toxic organic solvents is one of the
most important issues in green chemistry [1–3]. Their use in
organic synthesis inevitably leads to solvent emission and/or
waste. Especially, fluorination reactions have been recog-
nized as being useful in organic synthesis, their reactions
commonly employed organic solvents (such as DMF,
CH3CN, DMSO, etc.), and in many cases they are removed
from the final reaction mixture by a water quench which
leads to an aqueous waste stream [4]. Recently, studies of
reusable media such as fluorous fluid [5] and ionic liquids
[6–10] are having an important impact on organic reactions.
Synthesis of mono and gem-difluorinated molecules using
[C8mim][PF6] ionic liquid as a recyclable solvent medium
with diethylaminosulfur trifluoride (DAST) as the fluorinat-
ing reagent, is reported [11]. In the fluorine chemistry,
replacements of safety handling are one of the most
important issues.
Fluorinated activated aromatic systems such as b-naphtol is
targets of important in the field of organofluorine compounds.
1,1-Difluoronaphthalen-2(1H)-one 3 are especially interesting
as synthetic intermediates and tools for elucidating biological
processes. In this context, a recent report described the access
to the target compounds via a direct fluorination of b-naphtol 1
by means of commercially available SelectfluorTM in
acetonitrile (Scheme 1) [12]. The method gave fairly good
results (yields 2, 55%, 3, 22% and 4, 12% with 1.1 eq
SelectfluorTM and yields 2, 19%, 3, 68%, 4, 10% with 2.1 eq
SelectfluorTM for fluorination 1.
In connection with our studies on electrophilic chemose-
lective fluorination, we now report the fluorination of b-naphtol
1 in various conditions including the use of ionic liquids as
solvents. Ionic liquids present many advantages in the green
chemistry context and we assumed that they could be powerful
solvents for electrophilic fluorination since SelectfluorTM is a
charged compound. Ionic liquids as solvents are much polar
than classical organic solvents such as acetonitrile. So, 2-
naphtol much better can tautomerise to keto form in ionic
liquids. In conclusion, we will have a high regioselectivity in
the fluorination of 2-naphtol in ionic liquids as compared with
low regioselectivity in acetonitrile. Our results are reported in
Table 1. Interestingly, very high conversions were observed.
The reaction in ionic liquid minimises the protonated b-naphtol
1. When using methanol or ethanol as cosolvent. Thus, both
In this paper, we would like to describe the utility of ionic
liquids as a solvent for fluorination in good yields without the
need for conventional aqueous work-up procedures.
* Tel.: +98 242522 4021; fax: +98 242522 6932.
E-mail address: heravimr@yahoo.com.
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.11.006

218
M.R.P. Heravi / Journal of Fluorine Chemistry 129 (2008) 217–221
Scheme 1.
Table 1
Electrophilic fluorination b-naphtol 1 in ionic liquids
SelectfluorTM (eq)
Solvent
Cosolvent (1/1)
T (8C)
Time (h)
Yield 2 (%)a
Yield 3 (%)a
Yield 4 (%)a
1.1
1.1
1.1
1.1
1.1
Acetonitrileb
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
–
rt
6
1
1
3
3
55
97
98
98
94
22
2
12
1
MeOH
MeOH
EtOH
EtOH
20
20
20
20
2
0
2
0
3
1
2.1
2.1
2.1
2.1
2.1
Acetonitrileb
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
–
rt
7
1
1
3
3
19
1
68
98
99
98
97
10
1
MeOH
MeOH
EtOH
EtOH
20
20
20
20
1
0
2
0
2
1
a
Isolated yield.
b
Data taken from Ref. [12].
chemoselectivity and yield appear to be highly increased when
using ionic liquid as solvent (Scheme 1, Table 1).
(yields 6, 97%, 3, 2% and 7, 0% with 1.1 eq SelectfluorTM and
yields 6, 2%, 3, 98%, 7, 0% with 2.1 eq SelectfluorTM for
fluorination 5 (Scheme 2, Table 2).
N-(Naphthalen-2-yl)acetamide 5 showed similar behaviour
with SelectflourTM (1.1 eq) in ionic liquids, forming pre-
dominantly N-(1-fluoronaphthalen-2-yl)acetamide 6 and lesser
amounts of 1,1-difluoronaphthalen-2(1H)-one 3 and N-(3-
fluoronaphthalen-2-yl)acetamide 7, and fluorination with
SelectflourTM (2.1 eq) in ion liquids, forming predominantly
1,1-difluoronaphthalen-2(1H)-one 3, lesser amounts of N-(3-
fluoronaphthalen-2-yl)acetamide 7 and N-(1-fluoronaphthalen-
2-yl)acetamide 6. The method gave fairly good results using the
best ionic liquid [bmim][PF6] with EtOH as cosolvent (1/1)
13-Methyl-7,8,9,11,12,13,14,15,16,17-decahydro-
6H-cyclopenta[a]phenanthrene-3,17-diol 8 reacted with
SelectflourTM (1.1 eq) in ionic liquids to give 2-fluoro-13-
methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopen-
ta[a]phenanthrene-3,17-diol 9 and 4-fluoro-13-methyl-7,8,
9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenan-
threne-3,17-diol 10. Using ionic liquid [bmim][BF4] with
MeOH as cosolvent (1/1) yields 9, 88%, 10, 11% with 1.1 eq
SelectfluorTM. Compound 9 is produced in higher yield from
Scheme 2.
Table 2
Electrophilic fluorination N-(naphthalen-2-yl)acetamide 5 in ionic liquids
SelectfluorTM (eq)
Solvent
Cosolvent (1/1)
T (8C)
Time (h)
Yield 6 (%)a
Yield 3 (%)a
Yield 7 (%)a
1.1
1.1
1.1
1.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
20
20
20
20
1
1
2
2
97
96
98
96
2
1
2.5
2
1.5
0
3
1
2.1
2.1
2.1
2.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
20
20
20
20
1
1
2
2
3
3
2
2
96
95
97
98
1
2
1
0
a
Isolated yield.

M.R.P. Heravi / Journal of Fluorine Chemistry 129 (2008) 217–221
219
Scheme 3.
Table 3
Electrophilic fluorination 13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol 8 in ionic liquids
SelectfluorTM (eq)
Solvent
Cosolvent (1/1)
T (8C)
Time (h)
Yield 9 (%)a
Yield 10 (%)a
1.1
1.1
1.1
1.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
20
20
20
20
0.5
0.5
1
87
88
82
86
11
11
12
10
1
a
Isolated yield.
Scheme 5.
Scheme 4.
Table 5
Electrophilic fluorination N-(anthracen-9-yl)acetamide 13 in ionic liquids
the reaction of 8 with SelectflourTM, Both fluorinated isomers 9,
10 were useful in the study of cancer therapy with estrogens
[15–17] (Scheme 3, Table 3).
SelectfluorTM
(eq)
Solvent
Cosolvent
(1/1)
T
Time
(h)
Yield
14 (%)a
( 8C)
1.1
1.1
1.1
1.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
30
30
30
30
0.5
0.5
0.5
0.5
96
97
91
92
N-(Phenanthren-9-yl)acetamide 11 fluorinated with Select-
flourTM in ionic liquids and produced 10,10-difluorophenanth-
ren-9(10H)-one 12 as main product. Using ionic liquid
[bmim][PF6] with MeOH as cosolvent (1/1) in optimization
condition, yield 69%, 12 at 5 h with 1.1 eq SelectfluorTM
(Scheme 4, Table 4).
a
Isolated yield.
N-(Anthracen-9-yl)acetamide 13 is not fluorinated with
SelectflourTM in ionic liquids; instead cause oxidation to
produce anthracene-9,10-dione 14. Using ionic liquid
[bmim][PF6] with MeOH as cosolvent (1/1) yields in
optimization condition, yield 96%, 14 at 0.5 h with 1.1 eq
SelectfluorTM (Scheme 5, Table 5).
N-(Benzo[c]phenanthren-5-yl)acetamide 15 and benzo[c]-
phenanthren-5-ol 16 react with SelectflourTM in ionic liquids to
give the 6,6-difluorobenzo[c]phenanthren-5(6H)-one 17. Using
ionic liquid [bmim][PF6] with MeOH as cosolvent (1/1) in
optimization condition, yields 56% and 67%, 17 at 8, 7 h with
1.1 eq SelectfluorTM (Scheme 6, Table 6).
Table 4
Electrophilic fluorination N-(phenanthren-9-yl)acetamide 11 in ionic liquids
SelectfluorTM
(eq)
Solvent
Cosolvent
(1/1)
T
Time
(h)
Yield
12(%)a
( 8C)
1.1
1.1
1.1
1.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
30
30
30
30
5
5
6
6
69
67
65
65
a
Scheme 6.
Isolated yield.

220
M.R.P. Heravi / Journal of Fluorine Chemistry 129 (2008) 217–221
Table 6
Electrophilic fluorination N-(benzo[c]phenanthren-5-yl)acetamide 15 and benzo[c]phenanthren-5-ol 17 in ionic liquids
Substrate
SelectfluorTM (eq)
Solvent
Cosolvent (1/1)
T ( 8C)
Time (h)
Yield 17 (%)a
16, 17
16, 17
16, 17
16, 17
1.1
1.1
1.1
1.1
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][BF4]
MeOH
MeOH
EtOH
EtOH
40
40
40
40
8, 7
56, 67
53, 58
51, 56
52, 54
8, 7
9, 11
10, 13
a
Isolated yield.
3. Experimental
[bmim][PF6] (2g) and CH3OH (2 g) was stirred for 1 h at
20 8C. The product was extracted with diethyl ether
(10 Â 20 ml), and ionic liquid was recovered, and then the
organic layer was dried over anhydrous MgSO4, on removal of
the solvent. 1-Fluoronaphthalen-2-ol (3) was purified by
column chromatography on silica gel using a mixture of
petroleum ether-ethyl acetate (10:2) as an eluent. mp 50 8C
(Ref. [13] mp 53–54 8C); 1H NMR (500 MHz, CDCl3) d ppm:
6.22 (td, J = 10.1, 2.7 Hz, 1H), 7.82 (dd, J = 6.7, 1.8 Hz, 1H),
7.53 (dd, J = 6.2, 2.6 Hz, 2H), 7.44 (d, J = 10.1 Hz, 1H), 7.37
(dd, J = 6.4, 2.0 Hz, 1H). 13C NMR (126 MHz, CDCl3) d ppm:
105.5 (t, J = 244.7 Hz, 1C), 123.4, 127.7, 129.9, 130.2, 131.0,
132.1, 133.2, 145.6, 187(C O). 19F NMR (235 MHz, CDCl3) d
ppm À101.51 (s, 1F). IR (neat, cmÀ1): 3144, 2997, 1688
(C O), 1572. HRMS (EI) found: M+, 180.0388; C10H6OF2
requires M+, 180.0401; LRMS m/z (EI): 180 (25% M+), 161
(100%); ES+: MNa+, 203, MH+, 181; Elemental analysis:
found (%): C, 66.50; H, 3.18; calcd. for C10H6OF2: C, 66.67; H,
3.36.
3.1. General
All commercially available reagents were without further
1
purification. Chemical shifts of H (500 MHz) and 13C NMR
(125 MHz) spectra were recorded using Bruker DRX500
machine at room temperature in ppm (d) and spectra were
measured using deuterochloroform as solvent using residual
solvent as an internal standard and CFCl3 as an internal
standard for 19F NMR. Mass spectra were obtained using a
Micro mass LCT machine in ES or EI mode. Infra-red spectra
were measured on a PerkinElmer Paragon100 FT-IR spectro-
photometer. Melting point was determined using a Liukam
HF591 heating stage, used in conjunction with a TC92
controller and are uncorrected. All reaction solvents used were
HPLC grade or distilled; petroleum ether refers to the fraction
which boils in the range 40–60 8C. TLC plates were visualized
by UV light (254 nm).
3.2. 1-Fluoronaphthalen-2-ol (2)
3.4. N-(1-Fluoronaphthalen-2-yl) acetamide (6)
mp 118–120 8C (Ref. [14] mp 120–121 8C); 19F NMR
(235 MHz, CDCl3) d ppm: À141.7 (s, 1F).
A mixture solution of 2-naphtol (1) (324 mg, 2 mmol) and
SelectfluorTM (365 mg, 1.1 mmol) in mixture of (1/1)
[bmim][PF6] (2 g) and CH3OH (2 g) was stirred for 1 h at
20 8C. The product was extracted with diethyl ether
(10 Â 20 ml), and ionic liquid was recovered, and then the
organic layer was dried over anhydrous MgSO4, on removal of
the solvent. 1-Fluoronaphthalen-2-ol (2) was purified by
column chromatography on silica gel using a mixture of
petroleum ether-ethyl acetate (10:2) as an eluent. mp 71 8C
3.5. 2-Fluoro-13-methyl-7,8,9,11,12,13,14,15,16,17-
decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol (9)
mp 174–175 8C (Ref. [15] mp 173–175 8C); 19F NMR
(235 MHz, CDCl3) d ppm: À138.4 (d, 1F).
1
(Ref. [13] mp 71–73 8C), H NMR (250 MHz, CDCl3) d ppm
3.6. 4-Fluoro-13-methyl-7,8,9,11,12,13,14,15,16,17-
decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol (10)
5.77 (s, 1H), 7.21 (t, J = 8.6 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H),
7.47 (t, J = 9.3 Hz, 2H), 7.72 (d, J = 8.2 Hz, 1H), 7.93 (d,
J = 8.4 Hz, 1H). 13C NMR (63 MHz, CDCl3) d ppm 94.2,
118.7, 118.8, 124.2, 126.6, 127.5, 129.0, 139.1 (d, J = 13.2 Hz),
142.8, 146.7. 19F NMR (235 MHz, CDCl3) d ppm À144.6 (s,
10 Hz, 6 Hz, 1F). IR (neat, cmÀ1): 3347, 3121, 1565. HRMS
(EI) found: M+, 162.0277; C10H7OF requires M+, 162.0316;
LRMS m/z (EI): 163 (25% M+), 162(100%); ES+: MNa+, 185,
MH+, 186; Elemental analysis: found (%): C, 73.89; H, 4.47;
calcd. for C10H7OF: C, 74.07; H, 4.35.
mp 189–190 8C (Ref. [15] mp 189–191 8C); 19F NMR
(235 MHz, CDCl3) d ppm: À137.0 (m, 1F).
3.7. 10,10-Difluorophenanthren-9(10H)-one (12)
Purification on alumina (benzene), mp 93–94 8C (Ref. [16]
mp 100–102 8C), 19F NMR (235 MHz, CDCl3) d ppm: À103.6
(S, 2F).
3.3. 1,1-Difluoronaphthalen-2(1H)-one (3)
3.8. Anthracene-9,10-dione (14)
A mixture solution of 2-naphtol (1) (324 mg, 2 mmol) and
SelectfluorTM (730 mg, 2.1 mmol) in mixture of (1/1)
mp 283–284 8C (authentic sample mp 283–284 8C).

M.R.P. Heravi / Journal of Fluorine Chemistry 129 (2008) 217–221
221
[3] (a) J. Earle, P.B. McCormack, K.R. Seddon, Chem. Commun. (1999)
2245–2246;
3.9. 6,6-Difluorobenzo[c]phenanthren-5(6H)-one (17)
(b) C.L. Adams, M.J. Earle, G. Roberts, K.R. Seddon, Chem. Commun.
(1998) 2087–2098;
1
Chromatography on alumina (benzene), mp 93–94 8C; H
NMR (500 MHz, CDCl3) d ppm 7.47–8.64 (m, ArH, 10H); 13
C
(c) P. Wasserscheid, W. Kwim, Angew. Chem. Int. Ed. Engl. 39 (2000)
3772–3789 (and references cited therein).
NMR (125, CDCl3) d ppm: 108.5 (t, J = 246 Hz), 121.5, 126.1,
126.7, 128.3, 128.7, 129.5, 130.6, 181.4 (C O). 19F NMR
(235 MHz, CDCl3) d ppm: À110.75 (S, 2F). HRMS m/z [M]+;
calcd. for C18H10F2O 280.0754, found: 280.0743. Elemental
analysis: found (%): C, 77.31; H, 3.64; calcd. for C18H10F2O:
C, 77.14; H, 3.57.
´
´
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In this study, I have demonstrated that modifications of
experimental conditions can either improved or modify the
electrophilic fluorination of activated aromatic systems. Worth
noting are the results obtained in ionic liquids, in which high
yields and chemoselectivity were observed. I am hopeful that
new useful fluorination in various fields will b born through our
fluorination technologies.
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Acknowledgements
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I thank Payame Noor University, Iran, for financial support
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spectra (special thanks from Prof. R.F.W. Jackson).
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