Synthesis and structure-activity relationship (SAR) of novel perfluoroalkyl-containing quaternary ammonium salts

Article abstract of DOI:10.1016/j.jfluchem.2005.08.004

A new series of perfluoroalkyl-containing quaternary ammonium compounds were prepared and examined for their antibacterial activities. The perfluoroalkyl-containing quaternary ammonium salts mainly exhibited excellent antibacterial activity for the Gram-p

Full text of DOI:10.1016/j.jfluchem.2005.08.004

Journal of Fluorine Chemistry 126 (2005) 1425–1431
www.elsevier.com/locate/fluor
Synthesis and structure-activity relationship (SAR) of novel
perfluoroalkyl-containing quaternary ammonium salts
Jian-Ying Sun a, Jing Li a, Xiao-Long Qiu b, Feng-Ling Qing a,b,
*
a College of Chemistry and Chemical Engineering, Donghua University, 1882 West Yanan Lu, Shanghai 20051, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 5 June 2005; received in revised form 21 July 2005; accepted 6 August 2005
Available online 15 September 2005
Abstract
A new series of perfluoroalkyl-containing quaternary ammonium compounds were prepared and examined for their antibacterial activities.
The perfluoroalkyl-containing quaternary ammonium salts mainly exhibited excellent antibacterial activity for the Gram-positive strain such
as Staphylococcus aureus, the MIC (minimal inhibitory concentration) values was between 2.5 and 10 mg/mL and the MBC (minimal
bactericidal concentration) values were 20 mg/mL. They all showed weak activity against the Gram-negative strain such as Escherichia coli,
and against fungi such as Candida albicans, the MIC values and MBC values were about 100 mg/mL. Moreover, the relationship between
their antimicrobial activities and structures were further discussed.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Perfluoroalkyl-containing compounds; Quaternary ammonium salt; Antibacterial activity
1. Introduction
firstly discovered to have marked antimicrobial activity in
1935 [9], which directly caused its wide research and
utilization in the past 70 years.
In daily life, people inevitably get in touch with many
kinds of microorganisms such as bacteria, fungi (yeasts,
molds, mildew) and algae, some of which can bring about
unpleasant odor, stain, and discoloration to fabric. One
important reason is that textiles are excellent medium for the
growth of microbes, which will be easily impregnated if the
suitable moisture and enough time are given. Thus, they
unassailably pose a threat to human health via breeding on
textiles. As the increasing demand for healthy living, it is
urgent to develop materials capable of killing harmful
microorganisms [1]. Recently, antibacterial finishing has
received more and more attention owing to their antibacter-
ial properties, and various antibacterial agents (such as
antiobiotics, silver ions, iodine and quarternary ammonium
compounds et al.) have been applied to the textiles [2–8].
The long-chain quaternary ammonium salt surfactants were
The antibacterial activity of quaternary ammonium
compounds is supposed to be due to their surface activity
properties. Recently, the perfluoroalkyl-containing com-
pounds and fluoropolymers have been shown to be effective
in application as repellent agents in textile finishing, which
worked by reducing the critical surface energy of fabrics
[10]. In addition, some fluoroalkyl end-capped compounds
with cationic segments such as trimethylammonium,
pyridinium [11,12], allylammonium [13,14], and dially-
lammonium groups, were also reported to be valid in
reducing the surface tension of water and oil with the
cationic surfactants. These fluorinated compounds also
exhibited antibacterial activity to some extent [11–14].
Our research group has recently reported on the synthesis
and antimicrobial activity of the perfluoroalkyl-containing
compound 1 (Fig. 1), which has good antibacterial activity
for Gram-positive strain (Staphylococcus aureus ATCC
6538) and Gram-negative strain (Escherichia coli 8099)
* Corresponding author. Fax: +86 21 64166128.
E-mail address: flq@mail.sioc.ac.cn (F.-L. Qing).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.08.004

1426
J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
Syntheses of compounds 3 and 4 started from perfluor-
oalkylated iodides 9 and 10, respectively (Scheme 2). The
first step proceeded by a free radical addition [16–18] of 9
and 10 to alkene 11 in the initiation of AIBN to provide the
fluoroalkylated iodides 12 and 13 in good yield, respectively.
Treatment of 12 and 13 with Zn dust and HCl gas [19]
resulted in one-step removal of iodine and acetyl group and
the desired alcohols 14 and 15 were furnished in 85% yield,
respectively. Tosylation of compounds 14 and 15 smoothly
gave the products 16 and 17, which further reacted with
diallylamine to produce the tertiary amines 18 and 19 in 95
and 80% yields. Finally, quaternary ammonium compounds
3 and 4 were obtained from the reaction of 18 and 19 with
CH3I in anhydrous CH3CN in 90 and 89% yields,
respectively.
Fig. 1. Structures of compounds 1–5.
[15]. In connection with our ongoing project about textile
finishing, we need to further investigate the structure-
activity relationship about some analogues of compound 1.
Here reported is our synthesis and antibacterial activity test
of a novel series of perfluoroalkyl-containing quaternary
ammonium salts 2–5, all of which are the analogues of our
reported compound 1. We have a preliminary comprehen-
sion about the impact of chain-length, halogen atoms and
nonfluoroalkyl chain on the antibacterial activity.
As to the synthesis of target compound 5, we firstly
attempted to prepare the key intermediate 25 from
chlorofluoroalkylated iodide 20 and allylic alcohol 21
(Scheme 3). However, treatment of compound 24 with
Bu3SnH/AIBN could not provide the alcohol 25. The
reaction was very complicated and in our opinion, reaction
failure was attributed to the existence of chlorine atom,
which involved in the free radical reaction. In addition,
attempt to remove iodine in 25 via LiAlH4 reduction [20]
only gave the desired product 25 in 10% yield. In view of
failure and low yield of above reactions, we decided to
construct the requisite hydroxyl group in 25 via hydrobora-
tion-oxidation of corresponding alkene. Thus, reaction of
chlorofluoroalkylated iodide 20 and allyl acetate 22 afforded
adduct 24, which was then converted into desired alkene 26
2. Results and discussion
We firstly synthesized out designed target molecules 2–5.
The alkyl-containing quaternary ammonium compound 2
was prepared as shown in Scheme 1. Treatment of alcohol 6
with TsCl in the presence of pyridine afforded tosylate 7 in
91% yield. Then, alkylation of diallylamine with 7 in the
presence of K2CO3 provided the desired compound 8 in 94%
yield, which was finally transformed to the desired molecule
2 as ammonium salts in 85% yield.
Scheme 1.
Scheme 2.

J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
1427
Scheme 3.
upon treatment with Zn/HCl. Hydroboration-oxidation of
alkene 26 gave the key intermediate 25 in 42% yield along
with the isomer 27 in 38% yield [21,22]. Finally, target
compound 5 was smoothly prepared from alcohol 25 via
tosylation and amination, followed by treatment of the
resulting amine 29 with CH3I.
With all designed quaternary ammonium compounds
1–5 in hand, we examined their antibacterial activity
against gram positive (S. aureus), gram negative (Escher-
ichia coli) and fungi (Candida albicans) microorganisms
on the basis of MIC (minimal inhibitory concentration)
values and MBC (minimal bactericidal concentration)
values. The results of antibacterial activity tests were
shown in Table 1.
superior to the perfluoroalkyl-containing compounds (1, 3,
4, 5).
Among these compounds with the same length of the
chains, such as 3, 5, and 1, the antibacterial activities of
compound 3 showed evident decline against S. aureus, the
MIC values rose from 2.5–5 mg/mL to 10 mg/mL. If we
change the end-capped fluorine atom into chlorine atom
(that is, from 1 to 5), the MIC values showed a little
difference. We get the similar result of the MIC values and
the MBC values when we kept the perfluoroalkyl-containing
groups (CF3(CF2)n-, n = 7) the same but increased the
number of spacer methylene groups from three to five (that is
from 1 to 4). It can be concluded that the influence of the
fluoroalkyl group is more effective than that of alkyl group
for antibacterial activity. In general, what we designed and
synthesized as perfluoroalkyl-containing quaternary ammo-
nium salts exhibit better properties than ecumenical ones. As
a kind of multifunctional finishing for textiles, these
compounds not only satisfy high demand for water, oil
and soil repellency, but also show good antibacterial
activities. However, the length of the chains does not have
an absolute connection with their antimicrobial activity.
The perfluoroalkyl-containing quaternary ammonium
salts (1, 3, 4 and 5) showed evident antibacterial activities
against gram-positive strain, which were even better than
their non perfluoroalkyl-containing counterpart 2. Their
antibacterial activities against Gram-negative strain were
low, whether these compounds have perfluoroalkyl-contain-
ing groups or not. However, the antibacterial activity against
the fungi strain of the long alkyl chain compound 2 is
Table 1
The MIC values and the MBC values for the compounds 1–5
Compound
MIC (mg/mL)
MBC (mg/mL)
S. aureus
E. coli
C. albicans
S. aureus
E. coli
C. albicans
ATCC 25923
ATCC 25922
ATCC 1600
ATCC 25923
ATCC 25922
ATCC 1600
1
2
3
4
5
2.5–5
20
>100
>100
100
50–100
50
20
40
20
20
20
>100
100
>100
50
10
100
100
>100
100
2.5
2.5
>100
>100
100
>100
>100
>100
>100

1428
J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
3. Experimental
1.87 (m, 2H), 3.27 (s, 3H), 3.39 (t, J = 6.8 Hz 2H), 4.27 (d,
J = 6.5 Hz, 4H), 5.75–5.91 (m, 4H), 6.00–6.10 (m, 2H).
Melting points were determined on a Pai-ke melting point
apparatus and were uncorrected. 1H NMR spectra were
recorded on a Bruker AM 400 (400 MHz) spectrometer with
Me4Si as an internal standard. 19F NMR spectra were
obtained on Bruker AM 400 (376 MHz) spectrometer in
CDCl3 with CFCl3 as an external standard, downfield shifts
being designated as negative. All chemical shifts (d) are
expressed in ppm, coupling constants (J) are given in Hz.
Mass spectra were recorded on a Finnigan-MAT-8430
instrument using EI ionization at 70 eV. IR spectra were
recorded on a Shimadzu IR-440 spectrometer.
3.4. 5-(Perfluorohexyl)-4-iodopentyl acetate (12)
Heating 4-pentenyl acetate 11 (0.44 g, 3.4 mmol) with
perfluorohexyl iodide 9 (3.02 g, 6.1 mmol) and AIBN
(50 mg) overnight at 95 8C under nitrogen until no raw
material was detected remaining by TLC. The gross product
was purified by column chromatography on silica gel
(petroleum ether:ethyl acetate = 20:1) to give compound 12
(1.47 g, 75%). 1H NMR (400 MHz, CDCl3) d: 1.65–1.79 (m,
4H), 2.05 (s, 3H), 2.78–2.89 (m, 2H), 4.11–4.14 (m, 2H),
4.33–4.38 (m,1H). 19F NMR (376 MHz, CDCl3) d: À80.83
(s, 3F), À112.04 to À111.25 (m, 2F), À121.81 (s, 2F),
À122.89 (s, 2F), À123.63 (s, 2F), À126.19 (s, 2F).
3.1. Toluene-4-sulfonic acid undecyl ester (7)
n-Undecanol (4.05 g, 23.5 mmol) and toluene-4-sulfonyl
chloride (6.22 g, 32.9 mmol) were dissolved in CHCl3
(50 mL), pyridine (4 mL) was then added, and the mixture
was stirred at room temperature until no alcohol was
detected remaining by TLC. The reaction mixture was
washed with water (20 mL), 2 M hydrochloric acid (20 mL)
and saturated NaHCO3 solution and brine. After drying
(Na2SO4) and filtrating, the solvent was evaporated and the
residue was purified by column chromatography on silica gel
(petroleum ether:ethyl acetate = 10:1) to give 3 as a white
3.5. 5-(Perfluorooctyl)-4-iodopentyl acetate (13)
Compound 13 (8.73 g, 85%) was prepared from 4-
pentenyl acetate 11 (1.96 g, 15.3 mmol), perfluorooctanyl
iodide 10 (10.44 g, 19.1 mmol) and AIBN (80 mg) using the
1
same conditions as described for compounds 12. H NMR
(300 MHz, CDCl3) d: 1.74–1.93 (m, 4H), 2.08 (s, 3H), 2.76–
3.00 (m, 2H), 4.13–4.16 (m, 2H), 4.37–4.39 (m, 1H). 19F
NMR (282 MHz, CDCl3) d: À81.34 (s, 3F), À111.65 to
À115.65 (m, 2F), À122.07 to À122.41 (m, 6F), À123.24 (s,
2F), À124.04 (s, 2F), À126.67 (s, 2F).
1
sheet solid (6.99 g, 91%). H NMR (400 MHz, CDCl3) d:
0.87 (t, J = 9.5 Hz 3H), 1.24 (s, 16H), 1.59–1.66 (m, 2H),
2.45 (s, 3H), 4.02 (t, J = 6.5 Hz, 2H), 7.34 (d, J = 8.0 Hz,
2H), 7.79 (d, J = 8.0 Hz, 2H).
3.6. 5-(Perfluorohexyl) pentanol (14)
3.2. N-(Undecyl)-N,N-diallylamine (8)
A HCl gas was bubbled through a suspension of Zn
powder (1.29 g, 19.7 mmol) and 5-(perfluorohexyl)-4-iodo-
pentyl acetate (3.77 g, 6.6 mmol) in ethanol (10 mL), until
the Zn powder was totally consumed. The mixture was then
refluxed until no compound 12 was detected by TLC. After
the removal of ethanol, the crude product was dissolved in
diethyl ether (25 mL), washed with brine, and concentrated.
The residue was purified by column chromatography on
silica gel (petroleum ether:ethyl acetate = 10:1) to give
compound 14 (2.28 g, 85%) as a yellow oil. 1H NMR
(400 MHz, CDCl3) d: 1.45–1.50 (m, 2H), 1.58–1.67 (m, 4H),
A
suspension of toluene-4-sulfonate
7
(6.55 g,
20.1 mmol), diallylamine (2.39 g, 24.6 mmol), and potas-
sium carbonate (3.40 g, 24.6 mmol) in anhydrous CH3CN
(30 mL) was heated to refluxing for 24 h under nitrogen. The
reaction mixture was filtered and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(petroleum ether:ethyl acetate = 20:1) to give compound 8
1
(4.24 g, 84%) as a colorless liquid. H NMR (400 MHz,
CDCl3) d: 0.87 (t, J = 6.6 Hz 3H), 1.26 (s, 16H), 1.43–1.49
(m, 2H), 2.40 (t, J = 6.8 Hz, 2H), 3.09 (d, J = 6.5 Hz, 4H),
5.12–5.19 (m, 4H), 5.81–5.91 (m, 2H).
1.79 (s, 1H), 2.05–2.09 (m, 2H), 3.69 (t, J = 6.4 Hz, 2H). 19
F
NMR (376 MHz, CDCl3) d: À80.81 (s, 3F), À114.41 (m,
2F), À121.96 (s, 2F), À121.90 (s, 2F), À123.56 (s, 2F),
À126.16 (s, 2F).
3.3. N-(Undecyl)-N,N-diallylmethyl ammonium iodide
(2)
A mixture of compound 8 (3.27 g, 13.0 mmol), CH3I
(3.69 g, 26.0 mmol) and anhydrous CH3CN (10 mL) were
stirred at 50 8C under nitrogen until no raw material was
detected remaining by TLC. The solvent was removed in
vacuo. The residue was washed with anhydrous ether
(3 Â 10 mL) to give the quaternary ammonium salt 2
(4.86 g, 95%) as a yellow solid. 1H NMR (400 MHz, CDCl3)
d: 0.88 (t, J = 6.6 Hz 3H), 1.26 (s, 12H), 1.32 (s, 4H), 1.80–
3.7. 5-(Perfluorooctyl) pentanol (15)
Compound 15 (4.33 g, 85%) was prepared as a white
solid from compound 13 (6.79 g, 10.1 mmol) and Zn powder
(1.88 g, 28.7 mmol) using the same conditions as described
1
for compounds 14. H NMR (300 MHz, CDCl3) d: 1.44–
1.52 (m, 2H), 1.57–1.70 (m, 2H), 2.05–2.11 (m, 2H), 3.68 (t,
J = 6.3 Hz, 2H). 19F NMR (282 MHz, CDCl3) d: À81.2 (s,

J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
1429
3F), À114.9 (m, 2F), À122.4 (s, 2F), À123.21 (s, 2F),
À124.0 (s, 2F), À126.6 (s, 2F).
on silica gel (petroleum ether:ethyl acetate = 12:1) to give
compound 18 (0.6 g, 95%) as a colorless oil. 1H NMR
(400 MHz, CDCl3) d: 1.38 (m, 2H), 1.51 (m, 2H), 1.61 (m,
2H), 2.05 (m, 2H), 2.44 (t, J = 3.2 Hz, 2H), 3.08 (d,
3.8. Toluene-4-sulfonic acid 6,6,7,7,8,8,9,9,10,10,
11,11,11-tridecanfluoro-undecyl ester (16)
J = 6.8 Hz, 4H), 5.13–5.20 (m, 4H), 5.81–5.91 (m, 2H). 19
F
NMR (376 MHz, CDCl3) d: À80.78 (s, 3F), À114.36 (m,
2F), À121.92 (m, 2F), À122.88 (m, 2F), À123.53 (s, 2F),
À126.14 (s, 2F). IR (thin film) 3080, 2947, 2800, 1644,
1419, 1240, 1145, 995, 920, 811, 707, 653 cmÀ1. MR m/z
100 (100), 41 (36), 42 (11), 68 (8), 69 (5), 55 (4). Anal.
Calcd. for C17H20F13N: C, 42.07; H, 4.15; N, 2.89. Found: C,
42.04; H, 4.12; N, 2.85%.
Alcohol 14 (2.72 g, 6.7 mmol) and toluene-4-sulfonyl
chloride (1.95 g, 10.2 mmol) were dissolved in CHCl3
(10 mL). Anhydrous pyridine (5 mL) was then added, and
the reaction mixture was stirred at room temperature until no
compound 14 was detected by TLC. The suspension was
decanted. The organic phase was washed three times with
water (30 mL), brine, dried over anhydrous MgSO4 and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (petroleum ether:ethyl acet-
ate = 10:1) to give compound 16 (2.40 g, 64%) as a white
solid. M.p. 42.5–43.5 8C; 1H NMR(300 MHz, CDCl3) d: 1.45
(m, 2H), 1.57 (m, 2H), 1.72 (m, 2H), 2.03 (m, 2H), 2.47 (s,
3H), 4.07 (t, J = 6.6 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.82 (d,
J = 8.1 Hz, 2H). 19F NMR (282 MHz, CDCl3) d: À81.66 (s,
3F), À115.32 (s, 2F), À122.84 (s, 2F), À123.79 (s, 2F),
À124.43 (s, 2F), 127.01 (s,2F). IR(thin film) 2962, 1599,
1479, 1360, 1260, 1174, 1142, 1047, 959, 840, 816, 698,
653 cmÀ1. MS m/z 173 (100), 172 (49), 155 (68), 91 (92),
65(34), 55 (23), 41 (20). Anal. Calcd. for C18H17F13SO3: C,
38.58; H, 3.06. Found: C, 38.45; H, 3.21%.
3.11. N-(6, 6, 7, 7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 13, 13,
13-Heptadecanfluorotridecyl)-N, N-diallylamine (19)
Compound 19 (1.10 g, 80%) was prepared as a colorless
oil from compound 17 (1.55 g, 2.3 mmol), diallylamine
(0.54 g, 5.5 mmol) and potassium carbonate (0.68 g,
4.9 mmol) using the same conditions as described for
compound 18. 1H NMR (400 MHz, CDCl3) d: 1.38 (m, 2H),
1.49 (m, 2H), 1.60 (m, 2H), 2.05 (m, 2H), 2.43 (t, J = 7.5 Hz,
2H), 3.08 (d, J = 6.5 Hz, 4H), 5.12–5.19 (m, 4H), 5.84 (m,
2H). 19F NMR (376 MHz, CDCl3) d: À80.76 (t, J = 11.3 Hz,
3F), À114.93 (m, 2F), À121.92 (m, 6F), À122.71 (s, 2F),
À123.53 (s, 2F), À126.10 (s, 2F). IR (thin film) 3080, 2946,
2801, 1643, 1419, 1241, 1208, 1149, 995, 920, 704,
655 cmÀ1. MS m/z 586 (M+ + 1, 4), 110 (100), 69 (3), 68 (4),
41 (28), 42 (8), 39 (6). Anal. Calcd. for C19H20F17N: C,
38.99; H, 3.44; N, 2.39. Found: C, 39.11; H, 3.42; N, 2.68%.
3.9. Toluene-4-sulfonic acid 6, 6, 7, 7, 8, 8, 9, 9, 10, 10,
11, 11, 12, 12, 13, 13, 13-heptadecanfluoro tridecyl ester
(17)
Compound 17 (1.75 g, 89%) was prepared as a white
solid from compound 15 (1.51 g, 3.0 mmol), TsCl (1.14 g,
6.0 mmol) and pyridine (3 mL) using the same conditions as
described for compounds 16. M.p. 50–52 8C. 1H NMR
(400 MHz, CDCl3) d: 1.42 (m, 2H), 1.55 (m, 2H), 1.68 (m,
2H), 2.03 (m, 2H), 2.45 (s, 3H), 4.05 (t, J = 3.4 Hz, 2H), 7.35
(d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H). 19F NMR
(376 MHz, CDCl3) d: À80.72 (t, J = 7.5 Hz, 3F), À114.41
(m, 2F), À121.73 (m, 6F), À122.69 (s, 2F), À123.50 (s, 2F),
À126.08 (s, 2F). IR (thin film) 2961, 2876, 1598, 1476,
1359, 1256, 1214, 1150, 1046, 961, 838, 814, 702,
656 cmÀ1. MS m/z 173 (82), 172 (48), 155 (62), 91
(100), 69 (22), 65 (38), 55 (24), 41 (24). Anal. Calcd. for
C20H17F17SO3: C, 36.38; H, 2.59. Found: C, 36.46; H,
2.81%.
3.12. N-(6,6,7,7,8,8,9,9,10,10,11,11,11-Tridecan-
fluoroundecyl)-N,N-diallylmethyl ammonium iodide (3)
A mixture of compound 18 (1.52 g 3.1 mmol), CH3I
(0.89 g, 6.3 mmol) and anhydrous CH3CN (8 mL) was
refluxed for 24 h under nitrogen. The solvent was removed
in vacuo. The residue was washed with anhydrous ether
(3 Â 10 mL) to give quaternary ammonium salt 3 (1.77 g,
90%) as a pale yellow dope. 1H NMR (400 MHz, CDCl3) d:
1.53 (m, 2H). 1.72 (m, 2H), 1.94 (m, 2H), 2.10 (m, 2H), 3.30
(s, 3H), 3.50 (m, 2H), 4.29 (m, 4H), 5.75–5.92 (m, 4H),
6.11–6.10 (m, 2H). 19F NMR (376 MHz, CDCl3) d: À80.83
(t, J = 9.8 Hz, 3F), À114.22 (s, 2F), À121.93 (m, 2F),
À122.90 (m, 2F), À123.46 (s, 2F), À126.15 (s, 2F). MS m/z
110 (9), 84 (100), 69 (6), 42 (23), 41 (51), 39 (22). IR (thin
film) 2954, 1640, 1467, 1203, 1145, 1050, 953, 732, 696,
653 cmÀ1. Anal. Calcd. for C18H23F13NI: C, 34.47; H, 3.70;
N, 2.23. Found: C, 34.27; H, 3.76, N, 2.21%.
3.10. N-(6,6,7,7,8,8,9,9,10,10,11,11,11-
Tridecanfluoroundecyl)-N,N-diallylamine (18)
A
suspension of toluene-4-sulfonate 16 (0.70 g,
3.13. N-(6, 6, 7, 7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 13,
13, 13-Heptadecanfluorotridecyl)-N, N-diallylmethyl
ammonium iodide (4)
1.3 mmol), diallylamine (0.27 g, 2.7 mmol), and potassium
carbonate (0.35 g, 2.6 mmol) in anhydrous CH3CN (10 mL)
was heated to reflux for 24 h under nitrogen. The reaction
mixture was filtered. The filtrates were concentrated in
vacuo. The residue was purified by column chromatography
Compound 4 (0.95 g, 89%) was prepared from compound
19 (0.87 g, 1.5 mmol) and CH3I (1.20 g, 8.5 mmol) using the

1430
J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
same conditions as described for compound 3. M.p. 61–
63 8C. 1H NMR (400 MHz, CDCl3) d: 1.51 (m, 2H), 1.71 (m,
2H), 1.90 (m, 2H), 2.11 (m, 2H), 3.30 (s, 3H), 3.50 (m, 2H),
4.27 (m, 4H), 5.77–5.90 (m, 4H), 5.60 (m, 2H). 19F NMR
(376 MHz, CDCl3) d: À80.74 (t, J = 7.5 Hz, 3F), À114.22 (t,
J = 15.0 Hz, 2F), À121.89 (m, 6F), À122.70 (s, 2F),
À123.41 (s, 2F), À126.08 (s, 2F). IR (thin film) 2954,
1640, 1476, 1204, 1150, 1051, 956, 871, 705, 657 cmÀ1. MS
m/z 168 (4), 110 (7), 85 (7), 84 (100), 69 (6). Anal. Calcd. for
C20H23F17NI: C, 33.03; H, 3.19; N, 1.93. Found: C, 33.20;
H, 3.12; N, 1.91%.
3.17. 11-Chloro-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-
cetanfluoro-1-hendecanol (25) and 11-Chloro-4,4,5,5,6,
6,7,7,8,8,9,9,10,10,11,11-cetanfluoro-2-hendecanol (27)
3.17.1. Synthesis of compound 25 from alcohol 23
A solution of 23 (5.05 g, 8.1 mmol) in anhydrous ether
(10 mL) was slowly added dropwise to a suspension of
LiAlH4 (0.45 g, 11.8 mmol) in anhydrous ether (15 mL)
during a 0.5 h at 35 8C, and the resulting mixture was stirred
for 20 h in reflux. Then ethyl acetate (5 mL) were added to
destroy excess LiAlH4 and diluent vitriol (2 mL, pH 6) were
added. After filtration, the mixture was extracted with ether
(3 Â 20 mL). After drying (Mg2SO4) and filtration, the
solvent was evaporated and the residue was purified by
column chromatography on silica gel (petroleum ether:ethyl
acetate = 10:1) to give compound 25 (0.41 g, 10%).
3.14. 11-Chloro-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-
Cetanfluoro-2-iodo-1-undecanol (23)
Compound 23 (12.35 g, 80%) was prepared from allyl
alcohol 21 (2.07 g, 35.7 mmol), iodide 20 (14.01 g,
24.9 mmol) and AIBN (100 mg) using the same conditions
as described for compounds 12. 1H NMR (400 MHz,
CDCl3) d: 2.02 (s, 1H), 2.73–3.05 (m, 2H), 3.77–3.87 (m,
2H), 4.42–4.46 (m, 1H). 19F NMR (376 MHz, CDCl3) d:
À68.01 (s, 2F), À112.91 to À113.4 (m, 2F), À120.08 (s, 2F),
À121.13 (s, 2F), À121.52 to À121.74 (m, 6F), À123.46(s,
2F).
3.17.2. Synthesis of compounds 25 and 27 from the
alkene 26
A solution of 26 (5.75 g, 12.1 mmol) in anhydrous THF
(15 mL) was slowly added dropwise to a solution of BH3Á
(CH3)2S (1 mL, 10 M in (CH3)2S) in THF (20 mL) at 10 8C
under nitrogen atmosphere. After stirring at room tempera-
ture for 3 h, 3 M NaOH (50 mL) and then 30% H2O2 (5 mL)
were added to the mixture at 20 8C. After further stirring for
2 h, water (80 mL) was added to the mixture. The mixture
was extracted with CH2Cl2 (3 Â 20 mL). After drying
(Mg2SO4) and filtrating, the solvent was evaporated in vacuo
and the residue was purified by column chromatography on
silica gel (petroleum ether:ethyl acetate = 5:1) to give
compound 25 (2.51 g, 42%) and compound 27 (2.29 g,
3.15. [3-(8-Chloro-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-
Cetanfluoro octyl)-2-iodo]propyl acetate (24)
Compound 24 (10.20 g, 82%) was prepared from allyl
acetate 22 (3.17 g, 31.3 mmol), iodide 20 (10.17 g,
22.0 mmol) and AIBN (80 mg) using the same conditions
as described for compounds 12. 1H NMR (400 MHz,
CDCl3) d: 2.12 (s, 3H), 2.75–2.97 (m, 2H), 4.28–4.37 (m,
1H), 4.38–4.47 (m, 2H). 19F NMR (376 MHz, CDCl3) d:
À68.31 (s, 2F), À113.32–114.03 (m, 2F), À121.36 (s, 2F),
À121.54 to À122.03 (m, 8F), À123.74(s, 2F).
1
38%). Compound 25: H NMR (300 MHz, CDCl3) d: 1.54
(s, 1H), 1.82–1.91 (m, 2H), 2.13–2.28 (m, 2H), 3.75 (t,
J = 12.0 Hz, 2H). 19F NMR (282 MHz, CDCl3) d: À68.37 (s,
2F), À114.67 (s, 2F), À120.46 (s, 2F), À121.81 (m, 8F),
À122.85(s, 2F). Compound 27: 1H NMR (300 MHz, CDCl3)
d: 1.33 (d, J = 6.6 Hz, 3H), 2.03 (s, 1H), 2.19–2.37 (m, 2H),
4.32–4.38 (m, 1H). 19F NMR (282 MHz, CDCl3) d: À68.41
(s, 2F), À113.60 (s, 2F), À120.49 (s, 2F), À122.17 to
À121.56(m, 8F), À124.01 (s, 2F).
3.16. 11-Chloro-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-
cetanfluoro-hendecane-1-ene (26)
The activated Zn powder (1.29 g, 19.7 mmol) was
suspended in isopropanol (15 mL). After the mixture was
heated to 70 8C, the mixture of 24 (9.26 g, 14.0 mL),
isopropanol (10 mL) and acetic acid (3 mL) were slowly
added dropwise. The resulting mixture was heated at 85 8C
with stirring for 2 h. Aqueous HCl (2.5 mL) was added and
the mixture was stirred for further 4 h at 80 8C to destroy
excess zinc. The resulting two phases were separated. After
removal of solvent in the organic phase, the residue was
purified by column chromatography on silica gel (petro-
leum ether:ethyl acetate = 100:0) to give compound 26
3.18. Toluene-4-sulfonic acid 11-chloro-
4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-cetanfluorohendecyl
ester (28)
Compound 28 (2.61 g, 87%) was prepared as a white solid
from compound 25 (2.30 g, 4.7 mmol), TsCl (1.38 g,
7.2 mmol) and pyridine (5 mL) using the same conditions
1
as described for compounds 16. M.p. 49–50 8C. H NMR
(400 MHz, CDCl3) d: 1.97 (m, 2H), 2.13(m, 2H), 2.46 (s, 3H),
4.12 (t, J = 5.9 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.80 (d,
J = 6.8 Hz, 2H). 19F NMR (376 MHz, CDCl3) d: À68.00 (t,
J = 15.0Hz, 2F), À114.46 (s, 2F), À120.08 (s, 2F), À121.14
(s, 2F), À121.72 (s, 6F), À123.43 (s, 2F). IR (thin film) 2958,
1627, 1599, 1449, 1361, 1210, 1191, 1150, 1043, 994, 841,
816, 696, 663 cmÀ1. MS m/z 173 (10), 172 (25), 155 (100), 91
1
(4.38 g, 66%). H NMR (300 MHz, CDCl3) d: 2.81–2.93
(m, 2H), 5.31–5.38 (m, 2H), 5.81–5.83 (m, 1H). 19F NMR
(282 MHz, CDCl3) d: À68.03 (s, 2F), À121.29 (s, 2F),
À128.22 (s, 2F), À129.23(s, 2F), À129.88 (s, 6F),
À131.20(s, 2F).

J.-Y. Sun et al. / Journal of Fluorine Chemistry 126 (2005) 1425–1431
1431
(81), 65 (19). Anal. Calcd. for C18H13F16ClSO3: C,33.32; H,
2.02. Found: C, 33.34; H, 2.04%.
sion were incubated for 16–18 h at 37 8C in the presence of
each compound in different concentrations, the fungi
bacterial suspensions were incubated for 24 h at 35 8C.
MIC was the lowest concentration of antibacterial agent
inhibiting the development of visible growth. MBC was the
lowest concentration of antibacterial agent bactericing the
development of visible growth.
3.19. N-(11-Chloro-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-
cetanfluoro hendecyl) -N, N- diallylamine (29)
Compound 29 (1.96 g, 91%) was prepared as a colorless
oil from compound 28 (2.43 g, 3.7 mmol), diallylamine
(0.83 g, 8.5 mmol) and potassium carbonate (1.01 g,
7.3 mmol) using the same conditions as described for
compound 18. 1H NMR (400 MHz, CDCl3) d: 1.75 (m, 2H),
2.11 (m, 2H), 2.50 (t, J = 7.2 Hz, 2H), 3.08 (d, J = 6.4 Hz,
4H), 5.13–5.20 (m, 4H), 5.83 (m, 2H). 19F NMR (376 MHz,
CDCl3) d: À68.01 (t, J = 12.0 Hz, 2F), À114.12 (s, 2F),
À120.11 (s, 2F), À121.17 (s, 2F), À121.75 (s, 6F), À123.44
(s, 2F). IR (thin film) 3081, 2981, 2809, 1643, 1420, 1380,
1216, 1153, 996, 922, 734, 701, 648, 556cmÀ1. MS m/z 110
(100), 91 (8), 85 (9), 69 (9), 41 (29). Anal. Calcd. for
C17H16F16ClN: C, 35.59; H, 2.81; N, 2.44. Found: C, 35.30;
H, 2.71, N, 2.61%.
Acknowledgement
We thank the National Natural Science Foundation of
China, Ministry of Education of China and Shanghai
Municipal Scientific Committee for funding this work.
References
[1] G. Tanchis, Tanctoria 99 (2002) 68–69.
[2] M.K. Beliakova, A. Hebeish, Am. Dyestuff Reporter 3 (1998) 46–49.
[3] M.C. Thiry, S. Writer, AATCC Org. 11 (2001) 11–17.
[4] Y.J. Jeong, S.Y. Cha, W.R. Yu, W.H. Park, Textile Res. J. 72 (2002) 70–
76.
3.20. N-(11-Chloro-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11-
cetanfluoro hendecyl)-N, N-diallylmethyl ammonium
iodide (5)
[5] K. Teraoka, T. Nonami, Y. Yokogawa, H. Taoda, T. kameyama, J.
Mater. Res. 15 (2000) 1243–1244.
[6] Y.H. Kim, G. Sun, Textile Res. J. 71 (2001) 318–323.
[7] T. Nakashima, Y. Sakagami, H. Ito, M. Matsuo, Textile Res. J. 71
(2001) 688–694.
Compound 5 (2.17 g, 95%) was prepared from compound
29(1.82 g, 3.2 mmol)andCH3I (1.57 g, 11.1 mmol)usingthe
same conditions as described for compound 3. M.p. 98.5–
[8] J.D. Payne, D.W. Kudner, Am. Dyestuff Reporter 85 (1996) 26–30.
[9] G. Domagk, Dtsch. Med. Wochenschr. 61 (1935) 829–832.
[10] D. Lammermann, Melliand Textillber. Eng. Ed. 72 (1991) 380–
383.
1
100 8C. H NMR (400 MHz, CDCl3) d: 2.21–2.37 (m, 4H),
3.34 (s, 3H), 3.71 (m, 2H), 4.30 (m, 4H), 5.78–5.91 (m, 4H),
6.05 (m, 2H). 19F NMR (376 MHz, CDCl3) d: À68.04 (t,
J = 11.3 Hz, 2F), À113.41 (t, J = 15.0 Hz, 2F), À120.08 (s,
2F), À121.11 (s, 2F), À121.72 (m, 6F), À123.09 (s, 2F). IR
(thin film) 2967, 1632, 1476, 1438, 1384, 1204, 1149, 1113,
1094, 998, 954, 850, 702, 656 cmÀ1. MS m/z 168(5), 110 (5),
84 (100), 42 (11), 39 (9). Anal. Calcd. for C18H19F16ClNI: C,
30.21; H,2.68; N, 1.96. Found: C, 29.97; H, 2.76; N, 1.84%.
[11] H. Sawada, A. Wake, M. Oue, T. Kawase, Y. Hayakawa, Y. Min-
oshima, M. Mitani, J. Colloid Interface Sci. 178 (1996) 379–381.
[12] H. Sawada, A. Wake, T. Maekawa, T. Kawase, Y. Hayakama, T.
Tomita, M. Baba, J. Fluorine Chem. 83 (1997) 125–131.
[13] H. Sawada, K. Tanba, M. Oue, T. Kawase, Y. Hayakama, M. Mitani, Y.
Minoshima, M. Nishida, Y. Moriya, Polymer 36 (1995) 2103–2105.
[14] H. Sawada, K. Tanba, T. Tomita, T. Kawase, M. Baba, T. Ide, J.
Fluorine Chem. 84 (1997) 141–144.
[15] H. Shao, L. Jiang, W.-D. Meng, F.-L. Qing, J. Fluorine Chem. 124
(2003) 89–91.
3.21. Antimicrobial assessment
[16] N.O. Brace, J. Org. Chem. 27 (1962) 3033–3038.
[17] N.O. Brace, J. Fluorine Chem. 20 (1982) 313–327.
[18] J. Greiner, A. Milius, J.G. Riess, J. Fluorine Chem. 56 (1992) 285–293.
[19] C.-Y. Guo, S.-D. Wang, You Ji Hua Xue 14 (1994) 171–176.
[20] F.-L. Qing, M. Ji, R. Lu, K. Yan, Z. Mao, J. Fluorine Chem. 113 (2002)
39–141.
The antimicrobial activities were evaluated against S.
aureus ATCC 25923, E. coli ATCC 25922 and another yeast
strain of C. albicans ATCC 1600 by viable cell counting
method.
[21] P.V. Ramachandran, M.P. Jennings, Chem. Commun. (2002) 386–387.
´ `
[22] F.D. Campo, D. Lastecoueres, J.M. Vincent, J.B. Verlhac, J. Org.
MIC values and MBC values were determined by a
standard microdilution method. Common bacterial suspen-
Chem. 64 (1999) 4969–4971.