Synthesis and comparison of N-fluorobis[(perfluoroalkyl)sulfonyl]imides with different perfluoroalkyl groups

Article abstract of DOI:10.1016/S0022-1139(01)00463-8

N-fluorobis[(perfluoroalkyl)sulfonyl]imides, CF₃SO₂N(F)SO₂R_f (R_f′=C₄F₉, C₆F₁₃, C₈F₁₇) and (C₄F₉SO₂)₂NF, were prepared by direct fluorination of corresponding N-H compounds using elemental fluorine without a solvent in good to excellent yields. All of these N-F compounds are electrophilic fluorination agents and can easily deliver F⁺ to certain molecules. Their reactions with aromatic rings, beta-diketones, and alkenes were investigated to compare their fluorination power.

Full text of DOI:10.1016/S0022-1139(01)00463-8

Journal of Fluorine Chemistry 111 ꢀ2001) 253±257
Synthesis and comparison of N-¯uorobis[ꢀper¯uoroalkyl)sulfonyl]imides
with different per¯uoroalkyl groups
Jie Zhang, Darryl D. DesMarteau*
Howard L. Hunter Chemistry Laboratory, Clemson University, Clemson, SC 29634-1905, USA
Received 9 May 2001; accepted 25 July 2001
Abstract
N-¯uorobis[ꢀper¯uoroalkyl)sulfonyl]imides, CF3SO2NꢀF)SO2Rf ꢀR0f ˆ C4F9, C6F13, C8F17) and ꢀC4F9SO2)2NF, were prepared by direct
¯uorination of corresponding N±H compounds using elemental ¯uorine without a solvent in good to excellent yields. All of these N±F
‡
compounds are electrophilic ¯uorination agents and can easily deliver ``F '' to certain molecules. Their reactions with aromatic rings, beta-
diketones, and alkenes were investigated to compare their ¯uorination power. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Electrophilic ¯uorination; N-¯uorosulfonimides
1. Introduction
2. Results and discussion
In the past 20 years, a lot of effort has been directed
towards discovering safer and more selective electrophilic
¯uorinating agents, which surmount some of the dif®cul-
ties associated with perchloryl ¯uoride, elemental ¯uorine
and hypo¯uorites. As a result of these efforts, a number
of N±F compounds have been synthesized and found to
be generally better sources of electrophilic ¯uorine
for selective ¯uorinations [1,2]. While many other elec-
trophilic N±F reagents have been developed and several
are commercial, none of these possess the reactivity
and utility of N-¯uorobis[ꢀper¯uoroalkyl)sulfonyl]imide
reagents [3].
The ®rst and simplest compound of this type was N-
¯uorobis[ꢀtri¯uoromethyl)sulfonyl]imide ꢀ1a) that was
synthesized and shown to work as an ef®cient reagent for
the selective ¯uorination of a variety of substrates [3]. It has
excellent long-term stability, desirable physical properties
and high reactivity [4±11].
2.1. Synthesis of N±F compounds
Bis[ꢀper¯uoroalkyl)sulfonyl]imides ꢀ2), the precursors
of 1, were prepared according to the synthetic route devel-
oped by us [12] as shown in Scheme 1. All steps except
the preparation of tri¯ic anhydride have excellent yields
ꢀ95±98%). Recently ꢀCF3SO2N)2Li is available from 3 M
Co and both the acid and lithium salt are available from
Aldrich. Bis[ꢀper¯uoroalkyl)sulfonyl]imides are extremely
hygroscopic, and all procedures should be carried out under
anhydrous conditions.
N-¯uorobis[ꢀper¯uoroalkyl)sulfonyl]imides were prepa-
red by the direct ¯uorination of corresponding N±H
precursors ꢀScheme 2).
In earlier preparation of 1a±b, Singh et al. [3] and Witz
et al. [12] introduced F2 in one portion into a stainless steel
bomb containing the N±H compound at À1968C. But some-
times an uncontrolled overreaction occurred during warm-
up, and led to low yields. An improved procedure in which
¯uorine gas is introduced in portions has replaced the
older method. In the ¯uorination of 30 g ꢀ107 mmol) of
2a 10% excess F2 was introduced in portions according to
Table 1 at À1968C. After each ¯uorine addition, the liquid
nitrogen bath was removed and the bomb was allowed to
warm to 228C and remain at 228C for several hours. After
¯uorination was complete, 1a±b were puri®ed by trap-to-
trap distillation after the removal of co-product HF by
forming NaHF2 with NaF.
In order to further study and evaluate the synthetic
potential of N-¯uorobis[ꢀper¯uoroalkyl)sulfonyl]imides,
a variety of RfSO2NꢀF)SO2R0f ꢀ1b±e) were synthesized.
Their reactivities in several selective ¯uorinations were
then compared.
* Corresponding author. Tel.: ‡1-864-656-4705; fax: ‡1-864-656-0627.
E-mail address: fluorin@clemson.edu ꢀD.D. DesMarteau).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 4 6 3 - 8

254
J. Zhang, D.D. DesMarteau / Journal of Fluorine Chemistry 111 22001) 253±257
Scheme 1.
could be due to a number of factors, including the structure
of the solid acid, lower solubility of the acid in the product
HF and perhaps low vapor pressure of the starting acid.
Originally we had reported that 1e could not be prepared at
228C [3]. Higher reaction temperatures were not attempted
based on the obviously incorrect assumption at that time that
heating would lead to degradation. In fact, all the N±F
compounds exhibit excellent thermal stability as determined
by DSC measurements. The onset of decomposition was: 1b
1908C; 1c 2008C; 1d 2058C; 1e 1508C. Clearly the stability
appears to be about the same as one Rf group increases in
size, but is lower with two larger Rf groups. Differences in
thermal stability may be due to the presence of a liquid phase
for a longer time in the small, sealed, stainless steel DSC
capsule for the larger Rf groups. For 1a, we have not
determined the decomposition under conditions where
liquid 1a would be present.
Scheme 2.
Table 1
Time table of fluorination of ꢀCF3SO2)2NH ꢀ107 mmol)
Time ꢀh)
Amount of F2 introduced ꢀmmol)
0
2
5
15
6
30
10
15
30
38 ꢀ118 total, 10% excess)a
2.2. Fluorination reactivity studies
a The bomb was allowed to stand at 228C for 8 h after this addition.
N-¯uorobis[ꢀtri¯uoromethyl)sulfonyl]imide ꢀ1a) is the
most reactive among known N±F compounds [13]. We
believe its ¯uorination power comes from the extraordinary
electron withdrawing ability of two CF3SO2 groups as
related to the acidity of the parent sulfonimide ꢀCF3SO2)2-
NH ꢀ2a). Koppel et al. [14] have measured the gas phase
acidity of many per¯uorinated sulfonimides and found that
2b±e were more acidic than 2a with ꢀC4F9SO2)2NH ꢀ2e)
presently holding the record as the strongest measured gas
phase superacid. We wondered if these acidity differences
might be re¯ected in the ¯uorination power of the corre-
sponding N±F compounds. Also of interest were the possible
steric effects of the larger RF groups on reactivity. Based
on the limited reactivity studies with these N±F agents
with 1,3-dicarbonyl derivatives, a,b-unsaturated carbonyl
compounds, and aromatic rings, we found no signi®cant
differences between the reactivity of 1a±e.
The same method was used to prepare 1c±e, and isolation
of the pure compounds was possible by removal of the HF
under vacuum at 08C, followed vacuum distillation from any
unreacted acid. The reaction of the N±H compounds
becomes much slower with increasing size of the Rf group
ꢀTable 2). Heating at 50±608C is necessary to obtain high
conversion of the acids to the N±F derivatives. Surprisingly,
the heating results in little or no degradation of the starting
acid or the N±F product. The marked difference in reactivity
Table 2
Preparation of N±F compounds
N±F compound
Fluorination conditions
N±F ꢀd)
Yield ꢀ%)
All of these N±F agents can readily undergo reaction
with neutral b-diketones and b-ketoesters in CH2Cl2 at
228C to afford predominantly mono-¯uorinated products
ꢀScheme 3). The solubility of 1c±e in CH2Cl2 was relatively
1b
1c
1d
1e
228C, ꢀ1 day
À32.4
À32.3
À32.3
À31.3
81
80
92
98
50±608C, ꢀ10 days
50±608C, ꢀ10 days
50±608C, ꢀ10 days

J. Zhang, D.D. DesMarteau / Journal of Fluorine Chemistry 111 22001) 253±257
255
Scheme 3.
low, but reaction proceeded readily. But for other much
slower reactions with a,b-unsaturated carbonyls, solubility
appeared to be the rate-determining factor. If CH2Cl2/
CH3COOH was used as solvent, reaction of trans-4-phe-
nyl-3-butene-2-one with 1e was much slower than the same
reaction with 1a. But when the solvent was changed to dry
CH3CN/CH3COOH, both reactions ®nished within 10 h.
All the reactions were carried out using one equivalent of
the N±F reagents, so mono-¯uorination was the major
product, with small amounts of di¯uorinated product formed
in the ¯uorination of substrate 3. In the reactions of sub-
strates 5 and 7, two major isomers ꢀerythro- and threo-) were
obtained, but separation was not carried out.
from internal CFCl3 for 19F NMR spectra. CDCl3 was the
solvent for 19F NMR as well as for 1H NMR, unless
otherwise noted. Mass spectra were measured with a Hewlett
Packard 5985B GC/MS spectrometer. Column chromato-
graphy was performed on silica gel ꢀ100±200 mesh).
3.1. Materials
Bis[ꢀper¯uoroalkyl)sulfonyl]imides ꢀ2a±e) were prepared
according to methods reported previously ꢀScheme 1). The
solvents used for the reactions were dried by standard
methods before use. Other commercially available com-
pounds were used without further puri®cation.
Activated aromatics such as phenol, toluene, aniline, etc.
can be smoothly ¯uorinated by 1a at 228C [3]. Here biphenyl
and diphenylmethane were compared with 1a and 1e in
dichloromethane and acetonitrile solvents. Again in acet-
onitrile the delivery of F to the aromatic ring is much faster
than that in CH2Cl2. Preference for o-¯uorination was obser-
ved in all cases with the o-/p- ratio ranging from 1.5 to 3.2.
3.2. General procedure for preparation of
N-fluorobis2perfluoroalkyl)sulfonimides 21a±b)
Inside a dry box, bis[ꢀtri¯uoromethyl)sulfyl]imide ꢀ2a)
ꢀ107 mmol) was placed into a 500 ml stainless steel bomb.
The bomb was cooled to À1968C and evacuated. Excess
¯uorine gas ꢀ118 mmol) was then introduced in portions
according to Table 1. After each addition of ¯uorine, the
liquid nitrogen bath was removed and the bomb was allowed
to warm to 228C. After the ®nal portion of F2 was intro-
duced, the bomb was kept at 228C for 8 h. The reactor was
then cooled to À1968C and excess F2 was removed under
dynamic vacuum through a soda-lime column. The remaining
mixture was vacuum transferred into another stainless steel
bomb containing10 g of NaFandshakenat 228C for ca. 5 min
3. Experimental section
IR spectra were taken as neat ®lms on KCl using a Perkin-
1
Elmer FT-IR spectrometer SPECTRUM 2000. H and 19F
NMR spectra were obtained on a Bruker AC-200 instrument
at 200.13 and 188.31 MHz, respectively. Chemical shifts are
1
given in ppm from internal TMS for H NMR spectra and

256
J. Zhang, D.D. DesMarteau / Journal of Fluorine Chemistry 111 22001) 253±257
to allow the complete absorption of HF by NaF. Then the pure
product was obtained as a colorless liquid by trap-to-trap
d À32.3 ꢀN±F), À72.3 ꢀ3F), À81.0 ꢀ3F), À105.8 ꢀ2F), À119.7
ꢀ2F), À121.7 ꢀ4F), À122.2 ꢀ2F), À123.2 ꢀ2F), À126.6 ꢀ2F);
1e: IR n ꢀcmÀ1) 1464ꢀs), 1351ꢀs), 1208ꢀvs), 1145ꢀs), 1025ꢀm),
845ꢀm), 801ꢀm), 739ꢀm), 699ꢀw), 651ꢀw), 570ꢀw); 19F
NMR d À31.3 ꢀN±F), À81.1 ꢀ3F), À106.0 ꢀ2F), À120.8
ꢀ2F), À126.2 ꢀ2F).
distillation ꢀ0, À70, À1968C; product in À708C trap); 1a: 19
F
NMR d À33.5 ꢀN±F), À72.0 ꢀ6F); 1b: IR n ꢀcmÀ1) 1465ꢀs),
1235ꢀvs), 2150ꢀs),1022ꢀw),889ꢀm),849ꢀm), 738ꢀw), 703)w),
638ꢀw), 584ꢀw); 19F NMR d À32.4 ꢀN±F), À72.3 ꢀ3F), À81.2
ꢀ3F), À106.0 ꢀ2F), À120.7 ꢀ2F), À126.1 ꢀ2F).
3.4. General procedure for fluorination of
ethyl 4-nitrobenzoylacetate
3.3. General procedure for preparation of
N-fluoroperfluoroalkylsulfonimides 21c±e)
Into a CH2Cl2 ꢀ15 ml) solution of ethyl 4-nitrobenzoyla-
cetate ꢀ3, 2.0 mmol) was added 0.1 g of anhydrous Na2CO3
and 2.0 mmol of N±F at 228C and the reaction mixture
was stirred for 8 h. The reaction mixture was diluted with
ethanol ꢀ10 ml) and water ꢀ50 ml), extracted by CH2Cl2
ꢀ10 ml  2 ml), rinsed with brine and dried over Na2SO4.
Pure ethyl 2-¯uoro-3-ꢀ40-nitrophenyl)-3-oxo-propanoate
ꢀ4) was obtained by column chromatography on silica gel
using hexane/ethyl acetate [9], 4: 19F NMR d À190.86
Inside a dry box, 2d ꢀ7.1 mmol) was placed into an 80 ml
stainless steel bomb. The bomb was cooled to À1968C and
evacuated. Excess ¯uorine gas ꢀ12.1 mmol) was then intro-
duced in one portion. After addition of ¯uorine, the liquid
nitrogen bath was removed and the bomb was heated to 50±
608C for 10 days. The bomb was cooled to À1968C and
excess ¯uorine was removed as above. The bomb was then
warmed to 08 in an ice-water bath and connected to a
dynamic vacuum through a FEP trap ꢀÀ1968C) for about
10 min. All of the product HF was transferred into that FEP
trap and pure N±F product remained inside the bomb as a
colorless liquid. 1c: IR n ꢀcmÀ1) 1464ꢀs), 1360ꢀw), 1235ꢀvs)
1150ꢀs) 1022ꢀw), 889ꢀm), 849ꢀm) 739ꢀw), 703ꢀw), 638ꢀw),
585ꢀw); 19F NMR d À32.3 ꢀN±F), À72.0 ꢀ3F), À81.1 ꢀ3F),
À105.8 ꢀ2F), À119.7 ꢀ2F), À121.8 ꢀ2F), À123.0 ꢀ2F),
À126.5 ꢀ2F); 1d: IR n ꢀcmÀ1) 1465ꢀs), 1233ꢀvs), 1152ꢀs),
986ꢀw), 861ꢀm), 733ꢀw), 707ꢀw), 659ꢀw), 584ꢀw); 19F NMR
2
ꢀd, JHF ˆ 48:4 Hz).
3.5. General procedure for fluorination of
a,b-unsaturated carbonyl compound
The N±F reagent ꢀ1.0 mmol) was dissolved in 2 ml of
solvent ꢀTable 3) and added dropwise into the solution
of a,b-unsaturated carbonyl compound. The mixture was
then stirred at 228C for the desired time. Simple column
Table 3
Selective fluorination using different N±F reagents
Substrate
N±F agent
Conditions ꢀ228C)
Reaction time
Products ꢀ%, ratio)
3
3
1a
1b
1c
1d
1e
1a
1b
1c
1e
1a
1e
1a
1e
1a
1e
1a
1e
1a
1e
1a
1e
CH2Cl2, Na2CO3
CH2Cl2, Na2CO3
CH2Cl2, Na2CO3
CH2Cl2, Na2CO3
CH2Cl2, Na2CO3
CH2Cl2/CH3COOH
CH2Cl2/CH3COOH
CH2Cl2/CH3COOH
CH2Cl2/CH3COOH
CH3CN/CH3COOH
CH3CN/CH3COOH
CH3CN/CH3COOH
CH3CN/CH3COOH
CH2Cl2
8 h
4 ꢀ80a, 100/7d)
4 ꢀ83a, 100/12d)
4 ꢀ77a, 100/8d)
4 ꢀ80a, 100/8d)
4 ꢀ80a, 100/10d)
6 ꢀ75b, 61/100e)
6 ꢀ81b, 48/100e)
6 ꢀ80c, 50/100e)
6 ꢀ75b, 60/100e)
6 ꢀ71b, 50/100e)
6 ꢀ74b, 50/100e)
8 ꢀ79b, 55/100e)
8 ꢀ80b, 54/100e)
10 ꢀ63c, 1.5f)
8 h
8 h
3
3
8 h
3
8 h
5
3 days
3 days
5
5
10 days ꢀincomplete)
5
10 days ꢀincomplete)
5
<10 h
<10 h
2 days
2 days
40 h
5
7
7
9
9
CH2Cl2
40 h
10 ꢀ28c, 1.7f)
9
CH3CN
40 h
10 ꢀ90c, 1.8f)
9
CH3CN
CH2Cl2
40 h
36 h
10 ꢀ97c, 2.3f)
11
11
11
11
12 ꢀ63c, 2.4f)
CH2Cl2
36 h
12 ꢀ34c, 2.5f)
CH3CN
36 h
12 ꢀ95c, 2.3f)
CH3CN
36 h
12 ꢀ94c, 3.2f)
a Isolated yields.
b Yields are based on NMR.
c NMR conversion as a ratio of fluorinated products to unreacted N±F.
d Ratio of mono-F/di-F based on NMR.
e Ratio of erythro-/threo- based on NMR.
f Ratio of o-/p- based on NMR.

J. Zhang, D.D. DesMarteau / Journal of Fluorine Chemistry 111 22001) 253±257
257
chromatography gave the mixture of erythro- and threo-
2
References
products [8]; 6: erythro-form 19F d À200.1 ꢀd-d-q, JHF
ˆ
3
4
51:2, JHF ˆ 25, JHF ˆ 5:3 Hz); threo-form 19F d À202.3
ꢀd-d-q, 2JHF ˆ 47:6, 3JHF ˆ26:9, 4JHF ˆ 5:3 Hz); 8: erythro-
[1] S. Rozen, Chem. Rev. 96 ꢀ1996) 1717.
[2] S.D. Taylor, C.C. Kotoris, G. Hum, Tetrahedron 55 ꢀ1999) 12431.
[3] S. Singh, D.D. DesMarteau, S.S. Zuberi, M. Witz, H.-M. Huang,
J. Am. Chem. Soc. 109 ꢀ1987) 7194.
2
3
form 19F d À200.3 ꢀd-d, JHF ˆ 46:9, JHF ˆ 25:2 Hz);
threo-form 19F d À202.8 ꢀd-d, 2JHF ˆ 47:5, 2JHF ˆ 24:7 Hz).
[4] Z.-Q. Xu, D.D. DesMarteau, Y. Gotoh, J. Chem. Soc., Chem.
Commun. ꢀ1991) 179.
3.6. General procedure for fluorination of
aromatic rings
[5] G. Resnati, D.D. DesMarteau, J. Org. Chem. 56 ꢀ1991) 4925.
[6] W.T. Pennington, G. Resnati, D.D. DesMarteau, J. Org. Chem. 57
ꢀ1992) 1536.
[7] Z.-Q. Xu, D.D. DesMarteau, J. Chem. Soc., Perkin Trans I ꢀ1992)
313.
The aromatic and the N±F reagent were dissolved into
10 ml of solvent and stirred at 228C for desired time. 19F
NMR followed this reaction and the conversion of N±F was
determined by 19F NMR integration; 10: 2-¯uoro-19F NMR
d À118.6, 4-¯uoro-19F NMR d À116.1; 12: 2-¯uoro-19F
NMR d À118.4, 4-¯uoro-19F NMR d À118.0.
[8] D.D. DesMarteau, Z.-Q. Xu, M. Witz, J. Org. Chem. 57 ꢀ1992)
629.
[9] Z.-Q. Xu, D.D. DesMarteau, Y. Gotoh, J. Fluorine Chem. 58
ꢀ1992) 71.
[10] G. Resnati, D.D. DesMarteau, J. Org. Chem. 57 ꢀ1992) 4281.
[11] W. Ying, D.D. DesMarteau, Y. Gotoh, Tetrahedron 52 ꢀ1996) 15.
[12] D.D. DesMarteau, M. Witz, J. Fluorine Chem. 52 ꢀ1991) 7.
[13] F.A. Davis, W. Han, C.K. Murphy, J. Org. Chem. 60 ꢀ1995) 4730.
[14] I.A. Koppel, R.W. Taft, F. Anvia, S.-Z. Zhu, L.-Q. Hu, K. Sung, D.D.
DesMarteau, L.M. Yagupolski, Y.L. Yagupolski, N.V. Ignat'ev, N.V.
Kondratenko, A.Y. Volkonskii, V.M. Vlasov, R. Natorio, P.-C. Maria,
J. Am. Chem. Soc. 116 ꢀ1994) 3047.
Acknowledgements
The ®nancial support of this research by the National
Science Foundation is gratefully acknowledged.