Effect of solvents on the selective electrofluorination of aromatic compounds containing active methylene groups

Article abstract of DOI:10.1016/S0022-1139(98)00267-X

Voltammetry and constant current electrolysis was used to study the oxidative fluorination of PhSCH2COOMe, PhSCH2CONH2, PhSCH2COOPh and PhCH2CN in solvent-free and Et3N*3HF and Et3N*3HF dissolved in CH3CN, THF, DME and sulfolane. Sulfolane, DME and THF containig Et3N*3HF show much lower oxidation limits when compared to CH3CN/Et3N*3HF. These compounds udergo simultaneous oxidation along with background oxidation processes. Solvent-free Et3N*3HF has a much wider anodic potential range for the oxidation of organic compounds. Selective electrofluorination of PhSCH2COOPh does not show significant solvent effects. THF and DME were found to be more efficient for the selective fluorination of PhSCH2CONH2 and PhCH2CN compared to CH3CN. - Keywords: Selective electrofluorination; Active methylene compounds; Solvent effects

Full text of DOI:10.1016/S0022-1139(98)00267-X

Journal of Fluorine Chemistry 92 (1998) 177±180
Effect of solvents on the selective electro¯uorination of aromatic
compounds containing active methylene groups
V. Suryanarayanan, M. Noel*
Central Electrochemical Research Institute, Karaikudi 630 006, India
Received 23 April 1998; accepted 28 August 1998
Abstract
Voltammetry and constant current electrolysis was used to study the oxidative ¯uorination of PhSCH2COOMe, PhSCH2CONH2,
PhSCH2COOPh and PhCH2CN in solvent-free Et3NÁ3HF and Et3NÁ3HF dissolved in CH3CN, THF, DME and sulfolane. Sulfolane, DME
and THF containing Et3NÁ3HF show much lower oxidation limits when compared to CH3CN/Et3NÁ3HF. These compounds undergo
simultaneous oxidation along with background oxidation processes. Solvent-free Et3NÁ3HF has a much wider anodic potential range for the
oxidation of organic compounds. Selective electro¯uorination of PhSCH2COOMe and PhSCH2COOPh does not show signi®cant solvent
effects. THF and DME were found to be more ef®cient for the selective ¯uorination of PhSCH2CONH2 and PhCH2CN compared to
CH3CN. # 1998 Elsevier Science S.A. All rights reserved.
Keywords: Selective electro¯uorination; Active methylene compounds; Solvent effects
1. Introduction
which inhibits further electrochemical oxidative ¯uorination
in CH3CN/Et3NÁ3HF [16,17]. Phenylacetonitrile (PhCH2CN)
does not show a distinct oxidation peak in CH3CN/
Et3NÁ3HF [1].
CH3CN has been the solvent of choice for selective
electro¯uorination, but other solvents such as sulfolane
[1], and methylene chloride [2,3] have also been used. There
are few reports on the effect of different solvents on selective
electrochemical ¯uorination processes [4±6]. Acetonitrile
(CH3CN), dimethoxy ethane (DME) and tetrahydrofuran
(THF) appear to be good solvents for this purpose. Dimethyl
formamide (DMF) and dioxane have also been evaluated.
The ef®ciency of ¯uorination in methylene chloride appears
to depend on the nature of the compound involved [2]. The
solvent-free supporting electrolytes namely Et3NÁ3HF [7±
10], Et4NF.nHF [11,12] and py.nHF [13±15] themselves
may also be employed as the electrolytic medium for
selective electro¯uorination.
The selective electrochemical ¯uorination of these com-
pounds was carried out in sulfolane, THF and DME contain-
ing 1 M Et3NÁ3HF. In addition, Et3NÁ3HF itself was also
evaluated as the solvent-supporting electrolyte system for
these compounds. The anodic potential limits in these
solvent supporting electrolyte media and the voltammetric
behaviour of these compounds in such media are also
reported in this work.
2. Experimental details
In the present study, the following compounds which
show widely different behaviour in CH3CN/Et3NÁ3HF med-
ium as reported earlier [16,17] are chosen to assess the
in¯uence of solvent on their selective electrochemical ¯uor-
ination behaviour. Methyl a-(phenylthio)acetate (PhSCH2-
COOMe) undergoes ef®cient selective ¯uorination in
CH3CN/Et3NÁ3HF whereas a-(phenylthio)acetamide (PhS-
CH2CONH2) gave rather poor yields. Phenyl a-(phenylthio)
acetate (PhSCH2COOPh) undergoes strong adsorption
The purity of the samples was checked by HPLC (Shi-
madazu LC 8-A) with Shim±Pack (4.0 mmÂ25 cm) ODS
column which has absorbance at 254 nm and 100% metha-
1
nol as eluent. H NMR spectra were taken with a Brucker
NMR spectrometer at 90 MHz with tetramethysilane (TMS)
as internal standard and CDCl3 as solvent. 19F NMR spectra
were taken with a Brucker 80 CY NMR spectrometer at
75.4 MHz with CFCl3 as standard and CDCl3 as solvent.
THF and CH3CN (HPLC grade), sulfolane and DME (AR
grade) were obtained from SRL, India. Et3NÁ3HF was
prepared by mixing Et3N and anhydrous HF (AHF) at
*Corresponding author. Tel.: +91-04565-23213; fax: +91-456522088.
0022-1139/98/$ ± see front matter # 1998 Elsevier Science S.A. All rights reserved.
P I I : S 0 0 2 2 - 1 1 3 9 ( 9 8 ) 0 0 2 6 7 - X

178
V. Suryanarayanan, M. Noel / Journal of Fluorine Chemistry 92 (1998) 177±180
low temperatures. Tetrabutylammonium perchlorate
(TBAP) was kept in a dessicator. Phenylthio compounds
such as PhSCH2COOMe, PhSCH2CONH2 and PhSCH2-
COOPh were prepared and have been characterised [18].
PhCH2CN was obtained from SRL, India.
Cyclic voltammetry was done in an undivided cell with Pt
wire as working electrode, Pt foil counter electrode and Pd/
H2 reference electrode at 25Æ18C [16]. Et3NÁ3HF itself was
used as supporting electrolyte. The electrochemical cell was
fabricated using high density polypropylene. A single com-
partment polypropylene cell of 50 ml capacity with a tight
®tting Te¯on cover with provision for working, counter and
reference electrodes and a gas inlet were used. The
immersed portion of the N2 gas inlet tube used for deaera-
tion, was made of ¯uoroethylene polypropylene (FEP).
Electrolysis was carried out at Pt anode and cathode
(9 cm2). The required quantity of Et3NÁ3HF (0.3 M for
CH3CN and 1 M for other solvents) was dissolved in the
selected solvents under dry conditions. To eliminate possi-
ble presence of moisture, pre-electrolysis was carried out at
3.0 V. During the time of preparative electrolysis, polarity
reversal was applied between the electrodes (time interval
10 s positive and 10 s negative). After the electrolysis,
Na2CO3 solution was added to the electrolyte until the
pH was neutral. The solution was poured into 200 ml of
water and extracted with ether. The ether layer was washed
with brine (150 ml), ether evaporated and the residue was
dried over anhydrous MgSO4. Purity and hence the yield of
¯uoro compound was calculated using HPLC with CH3OH
as eluent.
Fig. 1. Cyclic voltammograms for the oxidation of 50 mM of PhCH2CN
on Pt in Et3NÁ3HF at different V (mV s 1): (a) 20; (b) 40; (c) 80; (d) 160;
(e) 320.
ever, in all the other three solvents, namely sulfolane, DME,
and THF, a minimum of 1.0 M Et3NÁ3HF was found to be
necessary to obtain satisfactory conductivity. In these three
media, the anodic limit was also found to be low (Table 1).
In general, the anodic background current was found to
increase with increasing concentration of Et3NÁ3HF.
In solvent-free Et3NÁ3HF, even active methylene com-
pounds without an ±S± atom, such as PhCH2CN show well-
de®ned voltammetric responses (Fig. 1). A distinct irrever-
sible anodic peak is noticed around 2.1 V. The anodic peak
current is found to increase with square root of sweep rate
and concentration. Typical cyclic voltammograms of
PhSCH2COOMe in solvent-free Et3NÁ3HF systems are
shown in Fig. 2. The cyclic voltammograms are quite
similar to those obtained in CH3CN/Et3NÁ3HF [16,17].
The oxidation peak potential, however, is shifted by
300 mV towards the less positive region. It may thus be
concluded that PhSCH2COOMe undergoes more facile
oxidation in solvent-free Et3NÁ3HF when compared to
CH3CN/Et3NÁ3HF. The oxidation processes, however, are
quite similar in both media. A similar conclusion may also
be drawn regarding the voltammetric behaviour of
PhSCH2CONH2.
3. Results and discussion
3.1. Cyclic voltammetric investigations
Initially, cyclic voltammograms were recorded in all the
solvent-supporting electrolyte systems chosen in the
absence of reactant molecules to study the background
current levels and anodic potential limits. (Table 1). The
anodic potential limit in solvent-free Et3NÁ3HF for example
is only slightly lower than the conventional O.1 M TBAP/
CH3CN system. In CH3CN, even 0.1 M Et3NÁ3HF was
found to be suf®cient to give a fairly conducting medium
with satisfactory anodic limits of 2.54 V (Table 1). How-
Table 1
Anodic limits for solvent-supporting electrolytes on Pt electrodes
The cyclic voltammograms of PhSCH2COOPh in sol-
vent-free Et3NÁ3HF exhibit the sharp anodic peaks which
are typical of strong reactant adsorption. For this compound,
polishing of electrode becomes absolutely necessary
between each voltammetric recording to ensure reproduci-
bility. The effect of blocking adsorption is also clearly
noticed in multisweep cyclic voltammograms. In the second
and subsequent sweeps, the anodic peak current falls
No.
Solvent-supporting
electrolyte systems
Anodic potential
limit at 2 mA cm
2
1
2
3
4
5
6
0.1 M TBAP/CH3CN
Et3NÁ3HF
2.82
2.62
2.52
1.90
1.46
1.22
0.1 M Et3NÁ3HF/CH3CN
1.0 M Et3NÁ3HF/sulfolane
1.0 M Et3NÁ3HF/THF
1.0 M Et3NÁ3HF/DME

V. Suryanarayanan, M. Noel / Journal of Fluorine Chemistry 92 (1998) 177±180
179
3.2. Preparative electrolysis
Since distinct oxidations peaks are not noticed in sulfo-
lane, DME and THF, it is dif®cult to select the anodic
potential for constant potential electrolysis. Hence, constant
current electrolysis was carried out for all the four com-
pounds mentioned above in the four supporting electrolyte
systems under otherwise identical conditions. A constant
charge of 2F/mol with current density of 15 mA/cm2 was
passed. The mono¯uoro products obtained from the four
compounds were con®rmed by 1H NMR and 19F NMR. The
spectroscopic data were found to agree well with literature
values of PhSCHFCOOMe, PhSCHFCONH2, PhSCHF-
COOPh [19] and PhCHFCN [20]. The results obtained
are summarised in Tables 2 and 3. Table 2 summarises
the overall yield obtained in each solvent-supporting elec-
trolyte system. This parameter can also be affected by
polymerisation and further lead to di¯uoro derivative.
The percentage of unreacted substrate in the product mix-
ture for each experiment based on HPLC data are sum-
marised in Table 3. The following generalised conclusions
may be drawn from these tables.
Compounds such as PhSCH2COOMe, which undergoes
quite ef®cient selective ¯uorination in CH3CN/Et3NÁ3HF
medium itself, also appears to behave well in other solvent-
supporting electrolyte systems. The overall yield for the
compound, for example, is above 50% in all the given
media.
Fig. 2. Cyclic voltammograms for the oxidation of 50 mM of
PhSCH2COOMe on Pt in Et3NÁ3HF at different V (mVs 1): (a) 20; (b)
40; (c) 80; (d) 160; (e) 320.
For compounds such as PhSCH2COOPh, which show
strong adsorption and polymerisation effects in CH3CN/
Et3NÁ3HF medium [16,17], variation of solvent supporting
electrolyte system results in very little improvement in yield
signi®cantly. Quite similar blocking of adsorption effects
for this compound was also noticed in CH3CN/Et3NÁ3HF
medium [16,17].
Table 2
Selective electrofluorination of active methylene containing compounds in different solvent-supporting electrolytes
No.
Substrate (5 mmol)
Yields (%)
0.1 M Et3NÁ3HF
CH3CN
1.0 M Et3NÁ3HF
Et3NÁ3HF
Sulfolane
THF
DME
1
2
3
4
PhSCH2COOCH3
PhCH2CN
72
24
22
17
63
60
53
32
64
58
72
10
51
69
66
22
59
54
18
19
PhSCH2CONH2
PhSCH2COOPh
Table 3
Percentage of unreacted material at the end of electrolysis during the selective electrochemical fluorination of active methylene containing compounds in
different solvent-supporting electrolytes
No.
Substrate (5 mmol)
Unreacted materials (%)
0.1 M Et3NÁ3HF
CH3CN
1.0 M Et3NÁ3HF
Et3NÁ3HF
Sulfolane
THF
DME
1
2
3
4
PhSCH2COOCH3
PhCH2CN
2
43
22
14
21
20
9
21
15
0
23
10
0
13
39
50
40
PhSCH2CONH2
PhSCH2COOPh
50
10
56

180
V. Suryanarayanan, M. Noel / Journal of Fluorine Chemistry 92 (1998) 177±180
and ef®ciency. The yield of mono¯uoro compound does not
exceed 30% in any of the solvent-supporting systems inves-
tigated.
COOPh), solvent supporting electrolyte system exert little
in¯uence on the overall yield and ef®ciency.
Hence, the solvent-supporting electrolyte system appears
to be important only in those cases wherever the yield in
CH3CN/Et3NÁ3HF is low and polymerisation and adsorp-
tion effects are also low. In these cases, solvent supporting
electrolyte systems have a profound in¯uence on the overall
yield and ef®ciency. PhCH2CN and PhSCH2CONH2 are the
typical cases in this category. In the case of PhCH2CN, all
the solvent-supporting electrolyte systems give higher
yields of mono¯uoro derivative, when compared to
CH3CN/Et3NÁ3HF. In the case of PhSCH2CONH2, sulfo-
lane, THF and DME are found to be the better solvents for
ef®cient selective electrochemical ¯uorination.
The present experimental results, however, are not sig-
ni®cantly broad to understand the exact cause for the widely
different effects of solvent-supporting electrolyte systems
on the overall yield and ef®ciency. Many solvent properties
can in¯uence the overall ef®ciency. Some possible causes
are solubility of reactants, stability of cation radicals gen-
erated in the solvent, the nucleophilicity of the solvent,
molecule and the solubility of ¯uorinated product in the
solvent-supporting electrolyte system.
Acknowledgements
VS thanks CSIR, New Delhi, for the award of Research
Fellowships. The authors also thank Volkswagen Stiftung,
Germany, for the ®nancial support of this work. Thanks are
also due to Mr. S. Govindu for the analytical assistance.
References
[1] E. Laurent, B. Marquet, R. Tardivel, J. Fluorine Chem. 49 (1990)
115.
[2] A. Bensadat, G. Bodennee, E. Laurent, R. Tardivel, J. Fluorine
Chem. 20 (1982) 333.
[3] H. Benotmane, A. Bensadat, J. Soc. Alger. Chim. 1 (1991) 73.
[4] T. Fuchigami, A. Konno, K. Nakagawa, M. Shimojo, J. Org. Chem.
59 (1994) 5937.
[5] S. Narizuka, T. Fuchigami, J. Org. Chem. 58 (1993) 4200.
[6] S. Narizuka, H. Koshiyama, A. Konno, T. Fuchigami, J. Fluorine
Chem. 73 (1995) 121.
[7] J. Meurs, W. Eilenberg, Tetrahedron 47 (1991) 705.
[8] T. Fuchigami, S. Narizuka, A. Konno, Unpublished results.
[9] S. Hara, S.Q. Chen, T. Hatakeyama, T. Fukuhara, S. Tsuyoshi, M.
Sekiguchi, Y.N. Makabu, Tetrahedron Lett. 36 (1995) 6511.
[10] T. Haufe, J. Prakt. Chem. 338 (1996) 99.
[11] K. Kato, K. Momota, Nagoya Kogyo Gijutsu Kenkyusho Hokoku 44
(1996) 673 (CA 1996: 201264s).
4. Conclusion
The present investigation suggests that Et3NÁ3HF exhibits
poor electrolytic conductivity in solvents other than
CH3CN. Hence a minimum of 1 M Et3NÁ3HF is necessary
for voltammetric study as well as preparative electrolysis in
these media. The voltammetric investigations in solvent-
free Et3NÁ3HF, in the present study, indicate broad simila-
rities between the voltammetric behaviour of all these
compounds in this medium and in CH3CN/Et3NÁ3HF.
The oxidative mechanistic pathway does not appear differ-
ent in these two media. The yield and ef®ciency of these
compounds are, however, in¯uenced signi®cantly by the
solvent-supporting electrolyte system used. In the case of
more easily oxidisable compounds (PhSCH2COOMe) and
more easily polymerisable molecular species (PhSCH2-
[12] K. Momota, Yoyuch Oyobi Koon Kagaku 39 (1996) 7 (CA 1996:
12520953v).
[13] K. Makino, H. Yoshioka, J. Fluorine Chem. 39 (1988) 435.
[14] S.M. Lee, J.M. Roseman, C.B. Zartman, E.P. Morrison, S.J.
Harrison, C.A. Starkiewicz, W.J. Middleton, J. Fluorine Chem. 77
(1996) 65.
[15] K. Suda, K. Hotoda, M. Aoyugi, T. Takanmi, J. Chem. Soc., Perkin
Trans. I 11 (1995) 1327.
[16] V. Suryanarayanan, S. Chellammal, M. Noel, J. Fluorine Chem.
(1998), (in press).
[17] V. Suryanarayanan, Ph.D. Thesis, Alagappa University, Karaikudi,
(1998).
[18] D.J. Pasto, D. Mcmillan, T. Murphy, J. Org. Chem. 30 (1965)
2688.
[19] T. Fuchigami, M. Shimojo, A. Konno, J. Org. Chem. 60 (1995) 3459.
[20] E. Laurent, B. Marquet, R. Tardivel, Tetrahedron 45 (1989) 4431.