A convenient synthesis of N-functionalized perfluoroalkanesulfonamides

Article abstract of DOI:10.1080/10426500903362535

This article describes the synthesis of new N-functionalized perfluoroalkanesulfonamides (5) with two sulfonamides functionalities. Perfluoroalkanesulfonyl fluoride underwent a reaction with 2-chloroethylamine hydrochloride or 3-bromopropylamine hydrobromide to give N-(2-chloroethyl or 3-bromopropyl) perfluoroalkanesulfonamides (1). Reaction of (1) with potassium thiocyanate gave N-(2-thiocyanatoethyl or 3-thiocyanatopropyl) perfluoroalkanesulfonamides (3). The sulfonyl chloride derivatives (4) were prepared by reaction of 3 with sulfuryl chloride. In the last step, 4 reacted with ammonia to give the bis sulfonamides derivatives (5). The structures of all new compounds prepared were determined by ¹H, ¹⁹F, and ¹³C NMR spectroscopies and by HR-MS. Copyright

Full text of DOI:10.1080/10426500903362535

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Phosphorus, Sulfur, and Silicon and the
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A Convenient Synthesis
of N-Functionalized
Perfluoroalkanesulfonamides
Zohra Benfodda a , Franck Guillen b & Hubert Blancou a b
a Institut des Biomolécules Max Mousseron (IBMM) , UMR CNRS 5247
Université de Montpellier I et de Montpellier II , Montpellier, France
b S3F Chimie Université de Montpellier II , Montpellier, France
Published online: 25 Aug 2010.
To cite this article: Zohra Benfodda , Franck Guillen & Hubert Blancou (2010) A Convenient Synthesis
of N-Functionalized Perfluoroalkanesulfonamides, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:9, 1905-1914, DOI: 10.1080/10426500903362535
To link to this article: http://dx.doi.org/10.1080/10426500903362535
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Phosphorus, Sulfur, and Silicon, 185:1905–1914, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903362535
A CONVENIENT SYNTHESIS OF N-FUNCTIONALIZED
PERFLUOROALKANESULFONAMIDES
Zohra Benfodda,1 Franck Guillen,2 and Hubert Blancou1,2
1Institut des Biomole´cules Max Mousseron (IBMM), UMR CNRS 5247 Universite´
de Montpellier I et de Montpellier II, Montpellier, France
2S3F Chimie Universite´ de Montpellier II, Montpellier, France
This article describes the synthesis of new N-functionalized perfluoroalkanesulfonamides
(5) with two sulfonamides functionalities. Perfluoroalkanesulfonyl fluoride underwent a re-
action with 2-chloroethylamine hydrochloride or 3-bromopropylamine hydrobromide to give
N-(2-chloroethyl or 3-bromopropyl) perfluoroalkanesulfonamides (1). Reaction of (1) with
potassium thiocyanate gave N-(2-thiocyanatoethyl or 3-thiocyanatopropyl) perfluoroalka-
nesulfonamides (3). The sulfonyl chloride derivatives (4) were prepared by reaction of 3
with sulfuryl chloride. In the last step, 4 reacted with ammonia to give the bis sulfonamides
derivatives (5). The structures of all new compounds prepared were determined by 1H, 19F,
and 13C NMR spectroscopies and by HR-MS.
Keywords Alkylamine salts; N-functionalized perfluoroalkanesulfonamides; perfluoroalka-
nesulfonyl fluoride
INTRODUCTION
Sulfonamides are an important class of pharmaceutical compounds that exhibit a
wide spectrum of biological activities. This functional group constitutes the largest class
of antimicrobial drugs, diuretics, carbonic anhydrase inhibitors, anticonvulsants, hypo-
glycemics, antithyroids agents, and antitumor drugs, and they exhibit a number of other
biological activities as well.1–9 Furthermore, some of them have proved to be useful as
herbicides and plaguicides.10,11 These activities have increased interest in the synthesis of
sulfonamides.
The sulfonamides function has been widely studied in the carbohydrogenated com-
pounds around major applications such as hypoglycemic agents, antibiotics, and carbonic
anhydrase inhibitors. However investigations on polyfluoroalkanesulfonamides or perfluo-
roalkanesulfonamides with a long chain have not been carried out in the biological area.
Received 3 July 2009; accepted 23 September 2009.
We gratefully acknowledge the Ministe`re de l’Education Nationale et de la Recherche for its financial
support (Ph.D. grant to Z. Benfodda).
Address correspondence to Hubert Blancou, Institut des Biomole´cules Max Mousseron (IBMM), UMR
CNRS 5247 Universite´ de Montpellier I et de Montpellier II, CC1706, Place Euge`ne Bataillon 34095, Montpellier
cedex 05, France. E-mail: hubert.blancou@univ-montp2.fr
1905

1906
Z. BENFODDA ET AL.
Generally, these fluorinated sulfonamides have been investigated principally for their toxi-
city, environmental impact of surfactants, surface treatments for clothes, home furnishings,
and paper protection properties.12–15
Sulfonamides are usually prepared from substituted sulfonyl chlorides or anhydrides
in the presence of a base in an aprotic solvent.16–18
The N-functionalized perfluoroalkanesulfonamides may be synthesized from perflu-
oroalkanesulfonyl azides or from the sulfonyl fluorides with the corresponding primary
amine in the presence of a base.16,19–21
Recently, we have reported the synthesis of perfluoroalkanesulfonamides, and we
have studied the inhibition effects of these compounds on bovine carbonic anhydrase.22 In
continuation of our research on the synthesis of bioactive perfluoroalkanesulfonamides, we
describe in this article the multistep synthesis of new N-functionalized perfluoroalkanesul-
fonamides, which contain two sulfonamide groups, starting from perfluoroalkanesulfonyl
fluoride and alkylamine hydrochloridex or hydrobromides.
RESULTS AND DISCUSSION
The N-(2-chloroethyl or 3-bromopropyl) perfluoroalkanesulfonamides (1) were pre-
pared from the perfluoroalkanesulfonyl fluorides and suitable amine salts with triethylamine
(TEA) in EtOAc at 0◦C. It is interesting to note that the synthesis of sulfonamides deriva-
tives (1) leads to side products, which were identified as perfluoroalkanesulfonic acid (2)
(Scheme 1).
In each case, an excellent conversion of perfluoroalkanesulfonyl fluorides into N-(2-
chloroethyl or 3-bromopropyl) perfluoroalkanesulfonamides was observed. Recrystalliza-
tion of these compounds in an ethanol/water mixture (V/V, 90:10) gave the corresponding
N-(2-chloroethyl or 3-bromopropyl) perfluoroalkanesulfonamides (1a–d) with high purity
in moderate to good yields (Table I).
The formation of the perfluoroalkanesulfonic acid (2) was probably related to the
hydrolysis of the perfluoroalkanesulfonyl fluoride, which did not react in the presence of
water and an excess of TEA after the treatment of the crude product. The formation rate
was determined as a function of time using 19F NMR spectroscopy (Figure 1).
Table I Preparation of the N-(2-chloroethyl or 3-bromopropyl)-perfluoroalkanesulfonamides
Reactants
Amine salts
Products
RFSO2F
1
Conversiona (%)
Yieldb (%)
2
Conversiona (%)
C6F13SO2F
C8F17SO2F
C6F13SO2F
C8F17SO2F
Cl− +NH3(CH2)2Cl
Cl− +NH3(CH2)2Cl
Br− +NH3(CH2)3Br
Br− +NH3(CH2)3Br
b
d
a
c
93
90
93
91
71
51
55
46
a
b
a
b
7
10
7
9
aThe conversions were determined by 19F NMR spectrocopy (d6-acetone) after treatment of the crude product.
They were also determined by the relative integration of the functional CF2 signal of compounds 1a, 1b, 1c, 1d,
2a, and 2b by the formula (fi/Ni)/(ꢀfi/Ni) × 100, where fi represents the height integration of the functional CF2
signal and Ni the number of corresponding atom.
bAll these compounds 1 were crystallized in ethanol/water (V/V, 90:10) media.

1907

1908
Z. BENFODDA ET AL.
Figure 1 Formation rate of 1c and 1d. The conversions were determined by 19F NMR spectroscopy (d6-acetone)
after treatment of the crude product (the residue was diluted with water and EtOAc then washed with 1N HCl and
water). They were also determined by the relative integration of the functional CF2 signal respectively of 1c and
1d compared with that of the functional CF2 signal of C8F17SO2F.
The N-(3-bromopropyl) perfluoroalkanesulfonamides 1a and 1c reacted with potas-
sium thiocyanate in absolute ethanol at 100◦C for 4 h and yielded the desired N-(3-
thiocyanatopropyl) perfluoroalkanesulfonamides 3a and 3c in good yields (Scheme 1).
We also employed similar conditions (1.5 eq. of potassium thiocyanate in absolute
ethanol at 100◦C for 4 h) for the synthesis of N-(2-thiocyanatoethyl) perfluoroalkanesulfon-
amides 3b and 3d, but unfortunately the starting material 1b and 1d still remained unreacted
(Scheme 1). The chlorine atom was a less suitable leaving group than the bromine atom.
In order to find out the optimum conditions, the reactions of 1d with potassium
thiocyanate were examined under various reaction conditions (Table II). In each case, the
formation of 3b and 3d were determined by 1H NMR spectroscopy. When more than 1.5 eq.
of potassium thiocyanate in ethanol (protic and polar solvent), in acetone (aprotic and polar
solvent), or acetonitrile (aprotic and polar solvent) were used, there was no formation of the
desired product (3b and 3d). However, when we used 1.5 eq. of potassium thiocyanate in
DMF (solvent with a high dielectric constant) at 100◦C for 27 h, the reaction was complete.
DMF is a basic solvent that solvates specifically the K+ ions and leads to more reactivity of
the nucleophile −SCN. It is interesting to note that the reaction time is the same regardless
of the length of the F-alkylated chain studied (Table II).
The N-(2-thiocyanatoethyl or 3-thiocyanatopropyl) perfluoroalkanesulfonamides (3)
react with sulfuryl chloride in a mixture of acetic acid/water at 50◦C to lead to the corre-
sponding alkanesulfonyl chloride derivatives (4a–d) in good yields according to a method
developed in our laboratory.
In the last step, the N-functionalized perfluoroalkanesulfonamides (5a–d) were pre-
pared by reaction of 4 with gaseous ammonia in EtOAc in good yields. Compounds 5a–d

N-FUNCTIONALIZED PERFLUOROALKANESULFONAMIDES
1909
Table II Preparation of the N-(2-thiocyanatoethyl)-perfluoroalkanesulfonamides
Reactants
KSCN (eq.)
Products
1 (1 eq.)
Solvent
Ethanol
Reaction time (h)
3
Conversiona (%)
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1b
1b
1.5
1.5
1.5
1.5
10
1
4
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
3b
3b
0
0
0
0
0
0
0
0
0
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Acetone
Acetone
Acetone
Acetonitrile
Acetonitrile
Acetonitrile
DMF
12
22
22
100
4
25
25
4
25
25
23
27
23
27
10
1.5
1.5
10
1.5
1.5
10
1.5
1.5
1.5
1.5
0
0
0
92
100
93
100
DMF
DMF
DMF
aThe conversions were determined by 1H NMR spectroscopy (d6-acetone) after treatment of the crude product
(the residue was diluted with water and EtOAc and washed with water). They were also determined by the relative
integration of the functional CH2 signal of 3b and 3d compared, respectively, with that of the functional CH2
signal of 2b and 2d.
were recrystallized in an ethanol/water mixture (V/V, 90:10) and were characterized by 19F,
1H, 13C NMR spectroscopies and HRMS (Scheme 1).
CONCLUSION
In summary, we prepared new N-functionalized perfluoroalkanesulfonamides, which
contain two sulfonamides function by a multistep reaction starting from perfluoroalkane-
sulfonyl fluoride and alkylamine hydrochlorides or hydrobromides. They were obtained
in good yields, and they were characterized by 19F, 1H, and 13C NMR spectroscopies and
HRMS.
EXPERIMENTAL
Moisture-sensitive reactions were carried out under dry nitrogen. Different perfluo-
roalkyl sulfonyl fluorides were prepared according to a method developed in our labora-
tory.23,24 Solvents were distilled from the appropriate drying agents immediately prior to
use.
1H, 19F, and 13C NMR spectra were recorded at 300.13 MHz, 282.37 MHz, and 75.46
MHz, respectively, with a Bruker Avance 300 spectrometer; the chemical shifts are given
1
in ppm relative to Me4Si for the H and 13C, and CCl3F for 19F, as internal standards.
Coupling constants were given in Hz. Mass spectra and HRMS were recorded on a Jeol SX
102 spectrometer.
Melting points were recorded at atmospheric pressure, unless otherwise stated, on a
Stuart Scientific SMP3 apparatus and were uncorrected.

1910
Z. BENFODDA ET AL.
Synthesis of RFSO2NH(CH2)nX (1): General Procedure (GP1)
To a suspension of 3-bromopropylamine hydrobromide or 2-chloroethylamine hy-
drochloride (1 eq.) in anhydrous ethyl acetate, triethylamine (2 eq.) and perfluoroalkanesul-
fonyl fluoride (0.9 eq.) were added at 0◦C. The mixture was then stirred at room temperature
for 12 h, then poured into water and extracted with ethyl acetate. The organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product
was purified by crystallization from EtOH/H2O (90:10).
Synthesis of N-(3-bromopropyl)-perfluorohexanesulfonamide 1a. Com-
pound 1a (11.73 g, 55%) was obtained from 3-bromopropylamine hydrobromide (10.0 g,
45.7 mmol) according to the GP1.
1
Mp: 89–90◦C; H NMR (300.13 MHz, d6-acetone): δ:2.21 (m, 2H, CH2CH2Br),
3.62 (m, 4H, CH2CH2CH2Br), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz, d6-
acetone): δ: −126.80 (m, 2F, CF3CF2), −123.30 (m, 2F, CF3CF2CF2), −122.36 (m, 2F,
CF2(CF2)2SO2), −120.97 (m, 2F, CF2CF2SO2), −113.58 (m, 2F, CF2SO2), −81.66 (m,
3F, CF3); 13C NMR (75.46 MHz, d6-acetone): δ:30.6 (CH2), 34.1 (CH2-CH2-CH2), 43.7
(CH2), 108–120 (C6F13); MS (FAB−) m/z: 518.
Synthesis of N-(2-chloroethyl)-perfluorohexanesulfonamide 1b. Com-
pound 1b (12.63 g, 71%) was obtained from 2-chloroethylamine hydrochloride (5.0 g,
43.1 mmol) according to the GP1.
Mp: 100–101◦C; 1H NMR (300.13 MHz, d6-acetone): δ:3.65 (m, 4H, (CH2)2), 8.50
(m, 1H, NH); 19F NMR (282.37 MHz, d6-acetone): δ: −126.77 (m, 2F, CF3CF2), −123.30
(m, 2F, CF3CF2CF2), −122.37 (m, 2F, CF2(CF2)2SO2), −120.94 (m, 2F, CF2CF2SO2),
−113.60 (m, 2F, CF2SO2), −81.68 (m, 3F, CF3); 13C NMR (75.46 MHz, d6-acetone): δ:
42.9 (CH2), 44.8 (CH2), 108–120 (C6F13); MS (FAB−) m/z: 460.
Synthesis of N-(3-bromopropyl)-perfluorooctanesulfonamide 1c. Com-
pound 1c (11.76 g, 46%) was obtained from 3-bromopropylamine hydrobromide (10.0 g,
45.7 mmol) according to the GP1.
Mp: 100–101◦C; 1H NMR (300.13 MHz, d6-acetone): δ:2.21 (m, 2H, CH2CH2Br),
3.63 (m, 4H, CH2CH2CH2Br), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz, d6-
acetone): δ: −126.80 (m, 2F, CF3CF2), −123.25 (m, 2F, CF3CF2CF2), −122.36 (m, 6F,
(CF2)3(CF2)2SO2), −120.97 (m, 2F, CF2CF2SO2), −113.52 (m, 2F, CF2SO2), −81.68
(m, 3F, CF3); 13C NMR (75.46 MHz, d6-acetone): δ:30.5 (CH2), 34.2 (CH2-CH2-CH2),
43.7 (CH2), 108–120 (C8F17); MS (FAB−) m/z: 618.
Synthesis of N-(2-chloroethyl)-perfluorooctanesulfonamide 1d. Com-
pound 1d (21.97 g, 51%) was obtained from 2-chloroethylamine hydrochloride (10 g, 86.2
mmol) according to the GP1.
Mp: 120–121◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 3.75 (m, 4H, (CH2)2), 8.50
(m, 1H, NH); 19F NMR (282.37 MHz, d6-acetone): δ: −126.86 (m, 2F, CF3CF2(CF2)6-),
−123.41 (m, 2F, CF3CF2CF2(CF2)5-), −122.40 (m, 6F, CF3(CF2)2(CF2)3(CF2)2-),
−121.01 (m, 2F, CF3(CF2)5CF2CF2-), −113.73 (m, 2F, CF3(CF2)6CF2-), −81.86 (m, 3F,
CF3(CF2)7); 13C NMR (75.46 MHz, d6-acetone): δ: 44.1 (CH2), 46.9 (CH2), 108–120
(C8F17); MS (FAB−) m/z: 560.
Synthesis of of RFSO2NH(CH2)nSCN (3): General Procedure (GP2)
These compounds were prepared by reaction of potassium thiocyanate (1.5 eq.) with
either 1a and 1c (1 eq.) in absolute ethanol or 1b and 1d in DMF at 100◦C, for 4 h and 27 h,

N-FUNCTIONALIZED PERFLUOROALKANESULFONAMIDES
1911
respectively. After completion and cooling, all volatile parts of the mixture were removed
in vacuo. The residue was dissolved in EtOAc and washed successively with water and
brine. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under
reduced pressure to yield the corresponding alkyl thiocyanates, which were used in the next
step without any purification.
Synthesis of N-(3-thiocyanatopropyl)-perfluorohexanesulfonamide 3a.
Compound 3a (5.05 g, 84%) was prepared starting from 1a (6.3 g, 12.1 mmol) in absolute
ethanol (60 mL) according to the GP2.
Mp: 84–86◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 2.21 (m, 2H, CH2CH2CH2),
3.25 (m, 2H, CH2SCN), 3.55 (m, 2H, NHCH2), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz,
d6-acetone): δ: −126.78 (m, 2F, CF3CF2), −123.30 (m, 2F, CF3CF2CF2), −122.36 (m, 2F,
CF2(CF2)2S), −120.96 (m, 2F, CF2CF2S), −113.59 (m, 2F, CF2S), −81.68 (m, 3F, CF3);
13C NMR (75.46 MHz, d6-acetone): δ: 31.4 (CH2SCN), 31.6 (CH2), 43.0 (NHCH2), 112.7
(SCN), 108–120 (C6F13); MS (FAB−) m/z: 497.
Synthesis of N-(2-thiocyanatoethyl)-perfluorohexanesulfonamide 3b.
Compound 3b (4.77 g, 82%) was prepared starting from 1b (5.6 g, 12.1 mmol) in DMF
(50 mL) according to the GP2.
Mp: 115–117◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 3.25 (m, 2H, CH2SCN), 3.65
(m, 2H, NHCH2), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz, d6-acetone): δ: −126.90 (m,
2F, CF3CF2), −123.43 (m, 2F, CF3CF2CF2), −122.48 (m, 2F, CF2(CF2)2S), −121.04 (m,
2F, CF2CF2S), −113.54 (m, 2F, CF2S), −81.89 (m, 3F, CF3); 13C NMR (75.46 MHz, d6-
acetone): δ: 34.7 (CH2SCN), 44.6 (NHCH2), 112.0 (SCN), 107–121 (C6F13); MS (FAB−)
m/z: 522.
Synthesis of N-(3-thiocyanatopropyl)-perfluorooctanesulfonamide 3c.
Compound 3c (5.65 g, 63%) was prepared starting from 1c (9.22 g, 14.9 mmol) in ab-
solute ethanol (65 mL) according to the GP2.
Mp: 121–122◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 2.22 (m, 2H, CH2CH2CH2),
3.25 (m, 2H, CH2SCN), 3.55 (m, 2H, NHCH2), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz,
d6-acetone): δ: −126.80 (m, 2F, CF3CF2), −123.25 (m, 2F, CF3CF2CF2), −122.36 (m,
6F, (CF2)3(CF2)2S), −120.97 (m, 2F, CF2CF2S), −113.59 (m, 2F, CF2S), −81.68 (m,
3F, CF3SCN); 13C NMR (75.46 MHz, d6-acetone): δ: 30.7 (CH2SCN), 31.1 (CH2), 42.7
(NHCH2), 111.6 (SCN), 108–120 (C8F17); MS (FAB−) m/z: 597.
Synthesis of N-(2-thiocyanatoethyl)-perfluorooctanesulfonamide 3d.
Compound 3d (5.0 g, 78%) was prepared starting from 1d (6.2 g, 11.1 mmol) in DMF (55
mL) according to the GP2.
Mp: 118–120◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 3.38 (m, 2H, CH2SCN), 3.77
(m, 2H, NHCH2), 8.50 (m, 1H, NH); 19F NMR (282.37 MHz, d6-acetone): δ: −126.77 (m,
2F, CF3CF2), −123.28 (m, 2F, CF3CF2CF2), −122.25 (m, 6F, (CF2)3(CF2)2S), −120.90
(m, 2F, CF2CF2S), −113.43 (m, 2F, CF2S), −81.69 (m, 3F, CF3);13C NMR (75.46 MHz, d6-
acetone): δ: 34.7 (CH2SCN), 44.6 (NHCH2), 111.8 (SCN), 108–120 (C8F17); MS (FAB−)
m/z: 583.
Synthesis of of RFSO2NH(CH2)nSO2Cl (4): General Procedure (GP3)
Compounds 3a–d dissolved in a mixture of acetic acid (5 eq.) and water (1.5 eq.)
were stirred for 30 min at 50◦C. Sulfuryl chloride (SO2Cl2, 10 eq.) was added dropwise to
the reaction mixture at 50◦C. This reaction was accompanied by a strong emission of gases
(SO2 and Cl2), which were trapped with an aqueous solution of NaOH (1 M). The excess of

1912
Z. BENFODDA ET AL.
SO2Cl2, present in the media, was hydrolyzed by the dropwise addition of water. The crude
product was extracted three times with EtOAc. The combined organic extracts were washed
three times with water, dried over anhydrous Na2SO4, and concentrated, giving a crude
material alkanesulfonyl chlorides (4a–d), which could be used without any purification.
Synthesis of N-(3-sulfonylchloridepropyl)-perfluorohexanesulfonamide
4a. Compound 4a (4.59 g, 85%) was obtained from 3a (5.0 g, 10 mmol) according to the
GP3. The excess of SO2Cl2 was hydrolyzed by the addition of water (25 mL).
Mp: 114–119◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 2.41 (m, 2H, CH2CH2CH2),
3.65 (m, 2H, NHCH2), 4.22 (m, 2H, CH2SO2Cl), 8.50 (m, 1H, NH); 19F NMR (282.37
MHz, d6-acetone): δ: −126.81 (m, 2F, CF3CF2), −123.27 (m, 2F, CF3CF2CF2), −122.35
(m, 2F, CF2(CF2)2S), −120.94 (m, 2F, CF2CF2S), −113.48 (m, 2F, CF2S), −81.63 (m, 3F,
CF3);13C NMR (75.46 MHz, d6-acetone): δ: 26.6 (CH2), 42.8 (NHCH2), 62.8 (CH2SO2Cl),
108–120 (C6F13).
Synthesis of N-(2-sulfonylchlorideethyl)-perfluorohexanesulfonamide
4b. Compound 4b (4.28 g, 82%) was obtained from 3b (4.77 g, 9.9 mmol) according to
the GP3. The excess of SO2Cl2 was hydrolyzed by the addition of water (20 mL).
Mp: 104–106◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 4.10 (m, 2H, NHCH2), 4.45
(m, 2H, CH2SO2Cl);19F NMR (282.37 MHz, d6-acetone): δ: −126.76 (m, 2F, CF3CF2),
−123.28 (m, 2F, CF3CF2CF2), −122.34 (m, 2F, CF2(CF2)2S), −120.91 (m, 2F, CF2CF2S),
−113.44 (m, 2F, CF2S), −81.66 (m, 3F, CF3);13C NMR (75.46 MHz, d6-acetone): δ: 39.8
(NHCH2), 64.7 (CH2SO2Cl), 108–120 (C6F13).
Synthesis of N-(3-sulfonylchloridepropyl)-perfluorooctanesulfonamide
4c. Compound 4c (5.09 g, 88%) was obtained from 3c (5.42 g, 9.06 mmol) according
to the GP3. The excess of SO2Cl2 was hydrolyzed by the addition of water (25 mL).
Mp: 116–118◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 2.41 (m, 2H,
CH2CH2SO2Cl); 3.63 (m, 2H, NHCH2); 4.15 (m, 2H, CH2SO2Cl); 8.52 (m, 1H,
NH); 19F NMR (282.37 MHz, d6-acetone): δ: −126.73 (m, 2F, CF3CF2), −123.25 (m,
2F, CF3CF2CF2), −122.26 (m, 6F, (CF2)3(CF2)2S), −120.91 (m, 2F, CF2CF2S), −113.45
(m, 2F, CF2S), −81.64 (m, 3F, CF3);13C NMR (75.46 MHz, d6-acetone): δ: 25.41 (CH2),
41.60 (NHCH2), 61.59 (CH2SO2Cl), 108–120 (C8F17).
Synthesis of N-(2-sulfonylchlorideethyl)-perfluorooctanesulfonamide
4d. Compound 4d (2.74 g, 64%) was obtained from 3d (4 g, 6.85 mmol) according to the
GP3. The excess of SO2Cl2 was hydrolyzed by the addition of water (20 mL).
1
Mp: 134–136◦C; H NMR (300.13 MHz, d6-acetone): δ: 4.12 (m, 2H, NHCH2);
4.42 (m, 2H, CH2SO2Cl); 8.71 (m, 1H, SO2NH); 19F NMR (282.37 MHz, d6-acetone): δ:
−126.70 (m, 2F, CF3CF2), −123.22 (m, 2F, CF3CF2CF2), −122.27 (m, 6F, (CF2)3(CF2)2S),
−120.83 (m, 2F, CF2CF2S), −113.35 (m, 2F, CF2S), −81.64 (m, 3F, CF3);13C NMR (75.46
MHz, d6-acetone): δ: 40.55 (NHCH2), 65.08 (CH2SO2Cl), 108–120 (C8F17).
Synthesis of of RFSO2NH(CH2)nSO2NH2 (5): General Procedure (GP4)
The compounds 4a–d were dissolved in ethyl acetate (30 mL), and gaseous NH3 was
bubbled through the solution for 15 min at room temperature. The mixture was stirred at
room temperature for 30 min, then filtered. The organic layer was washed three times with
water and brine, dried over anhydrous Na2SO4, filtered, and evaporated. The crude product
was purified by crystallization from EtOH/H2O (90:10) to give the title compound.
Synthesis of N-(3-propylsulfonamide)-perfluorohexanesulfonamide 5a.
Compound 5a (3.55 g, 93%) was obtained from 4a (4 g, 7.41 mmol) according to the GP4.

N-FUNCTIONALIZED PERFLUOROALKANESULFONAMIDES
1913
Mp: 138–140◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 2.15 (m, 2H, CH2CH2CH2),
3.23 (m, 2H, CH2SO2NH2), 3.61 (m, 2H, NHCH2), 6.30 (m, 2H, NH2), 8.41 (m, 1H,
NH);19F NMR (282.37 MHz, d6-acetone): δ: −126.75 (m, 2F, CF3CF2), −123.28 (m, 2F,
CF3CF2CF2), −122.34 (m, 2F, CF2(CF2)2S), −120.94 (m, 2F, CF2CF2S), −113.51 (m,
2F, CF2S), −81.64 (m, 3F, CF3);13C NMR (75.46 MHz, d6-acetone): δ: 25.3 (CH2CH2),
43.0 (NHCH2), 51.8 (CH2SO2), 108–119 (C6F13); MS (FAB−) m/z:519; HRMS calcd for
C9H8O4N2F13S2: 518.9645; found 518.9635.
Synthesis of N-(2-ethylsulfonamide)-perfluorohexanesulfonamide 5b.
Compound 5b (3.90 g, 95%) was obtained from 4b (4.28 g, 8.14 mmol) according to
the GP4.
Mp: 149–151◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 3.42 (m, 2H, NHCH2), 3.85
(m, 2H, CH2SO2NH2), 6.60 (m, 3H, NH, NH2); 19F NMR (282.37 MHz, d6-acetone): δ:
−126.75 (m, 2F, CF3CF2), −123.27 (m, 2F, CF3CF2CF2), −122.32 (m, 2F, CF2(CF2)2S),
−120.92 (m, 2F, CF2CF2S), −113.51 (m, 2F, CF2S), −81.61 (m, 3F, CF3); 13C NMR (75.46
MHz, d6-acetone): δ: 40.4 (CH2), 55.4 (CH2), 108–119 (C6F13); MS (FAB+) m/z:507;
HRMS calcd for C8H8O4N2F13S2: 506.9718; found 506.9735.
Synthesis of N-(3-propylsulfonamide)-perfluorooctanesulfonamide 5c.
Compound 5c (3.22 g, 95%) was obtained from 4c (3.62 g, 5.66 mmol) according to the
GP4.
Mp: 158–160◦C; 1H NMR (300.13 MHz, d6-DMSO): δ: 1.90 (m, 2H, CH2CH2CH2),
3.01 (m, 2H, CH2SO2NH2), 3.32 (m, 2H, NHCH2), 6.85 (m, 2H, NH2), 9.65 (m, 1H,
NH); 19F NMR (282.37 MHz, d6-DMSO): δ: −126.62 (m, 2F, CF3CF2), −123.17 (m, 2F,
CF3CF2CF2), −122.13 (m, 6F, (CF2)3(CF2)2S), −120.69 (m, 2F, CF2CF2S); −113.49 (m,
2F, CF2S); −81.40 (m, 3F, CF3);13C NMR (75.46 MHz, d6-DMSO): δ: 25.5 (CH2CH2CH2),
42.8 (NHCH2), 52.0 (CH2SO2), 108–120 (C8F17); MS (FAB−) m/z: 619; HRMS calcd for
C11H8O4N2F17S2: 618.9654; found 618.9641.
Synthesis of N-(2-ethylsulfonamide)-perfluorooctanesulfonamide 5d.
Compound 5d (2.25 g, 93%) was obtained from 4d (2.5 g, 4 mmol) according to the GP4.
Mp: 161–162◦C; 1H NMR (300.13 MHz, d6-acetone): δ: 3.43 (m, 2H, NHCH2), 3.83
(m, 2H, CH2SO2NH2), 6.50 (m, 3H, NH, NH2);19F NMR (282.37 MHz, d6-acetone): δ:
−126.71 (m, 2F, CF3CF2), −123.22 (m, 2F, CF3CF2CF2), −122.24 (m, 6F, (CF2)3(CF2)2S),
−120.86 (m, 2F, CF2CF2S), −113.49 (m, 2F, CF2S), −81.61 (m, 3F, CF3);13C NMR (75.46
MHz, d6-acetone): δ: 39.1 (CH2), 54.2 (CH2), 108–120 (C8F17); MS (FAB+) m/z:607;
HRMS calcd for C10H8O4N2F17S2: 606.9815; found 606.9825.
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