Towards functional fluorous surfactants. Synthesis of hydrophilic fluorous 1,2,3-triazolylmethyl ethers and di(1,2,3-triazolylmethyl) ethers

Article abstract of DOI:10.1016/j.jfluchem.2011.07.002

Copper(I)-accelerated Huisgen-Meldal dipolar cycloaddition reactions between polyfluoroalkyl azides and propargyl ethers of n-octanol and of triethyleneglycol monomethyl ether exhibited variation in yield of 1,2,3-triazol-4-ylmethyl ethers. Microwave acce

Full text of DOI:10.1016/j.jfluchem.2011.07.002

Journal of Fluorine Chemistry 132 (2011) 898–906
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Towards functional fluorous surfactants. Synthesis of hydrophilic fluorous
1,2,3-triazolylmethyl ethers and di(1,2,3-triazolylmethyl) ethers
1
2
*
Dominic V. Francis, D. Howard Miles , Adnan I. Mohammed , Roger W. Read , Xiaobei Wang
School of Chemistry, University of New South Wales, UNSW, Sydney, NSW 2052, Australia
A R T I C L E I N F O
A B S T R A C T
Article history:
Copper(I)-accelerated Huisgen–Meldal dipolar cycloaddition reactions between polyfluoroalkyl azides
and propargyl ethers of n-octanol and of triethyleneglycol monomethyl ether exhibited variation in yield
of 1,2,3-triazol-4-ylmethyl ethers. Microwave acceleration, and in situ generation of the azides, provided
improvements in yield and efficiency. In contrast, very good yields of equivalent fluorous triazoles were
obtained from a range of n-alkyl azides with propargyl ethers of perfluorohexylethanol and of
perfluoroheptylmethanol through conventional copper(I)-promoted reactions. Together, the resulting
substances with systematic variations in polyfluoroalkyl and alkyl substituent length and position of
substitution, and degree of oxygen content, make up small libraries of hybrid fluorous 1,2,3-triazol-4-
ylmethyl ethers as candidates for study as hydrophilic fluorous surfactants. In addition, a pilot sample of
di(1,2,3-triazol-4-ylmethyl) ethers with 10-octyl-1-polyfluoroalkyl-substituents and 10-nonyl-1-per-
fluorooctylethyl substituents were synthesised for the first time in an effort to develop more functional,
fluorous surfactants.
Received 1 April 2011
Received in revised form 30 June 2011
Accepted 4 July 2011
Available online 12 July 2011
Keywords:
Fluorous chemistry
Microwave acceleration
Dipolar cycloaddition
Fluorous 1,2,3-triazoles
Triazolylmethyl ethers
Fluorous surfactants
ß 2011 Elsevier B.V. All rights reserved.
1. Introduction
expected behaviour [24,25]. Similar anomalies of unpredictable
behaviour had been reported by others for solutions of polyfluor-
There has been widespread interest in polymeric and other,
hybrid fluorous compounds because of the unique surface activity
and physical and biological properties of materials derived from
them [1–10]. Implicit in many reports has also been the potential
of the compounds for the carriage of added functionality [11].
Fluorous modifications of small molecules derived from hetero-
cycles have received less systematic attention as surfactants [11–
19], although many innovative applications of fluorous tagged
molecules have appeared [20], especially in terms of separation
strategies [21] and recyclable catalysts [22,23]. We have recently
outlined the potential of small fluorous heterocycles as surfactants
and participants in self-assembly [24], and have described the
synthesis of 1,2,3-triazoles [24,25] and tetrazoles [25] with one
perfluoroalkyl substituent and one n-alkyl substituent, as exam-
ples of such compounds. A study of the influence of members of
this library of heterocycles at various concentrations on the surface
tension of m-xylene, in the accompanying paper [26], revealed
considerable surface activity, but indicated some anomalies in the
ocarbon–hydrocarbon hybrid molecules in vaseline oil [27]. In this
case, it was suggested that the discrepancies were possibly
attributable to issues of viscosity. We have chosen to examine
the possibility that the unpredictable surface tension behaviour
was due to the combination of fluorophilic and lipophilic
components of the two quite different sets of heterocyclic and
non-heterocyclic compounds. For example, relatively simple and
non-polymeric, 1H-1,2,3-triazole derivatives in which there was a
perfluorobutylethyl, perfluorohexylethyl, or perfluorooctylethyl
substituent at position 1 on the ring, and an n-alkyl chain located at
position 4 on the ring, showed consistent behaviour when the n-
alkyl chain was 4 or 6 carbons in length, but very different
behaviour when the chain was 8 carbons in length. This was
irrespective of the fluorous chain length. Our interest therefore
turned to analogues of the fluorous heterocyclic molecules in
which the partner group was more hydrophilic.
This paper describes the synthesis of fluorous 1,2,3-triazole
analogues in which the 1-polyfluoroalkyl group is retained and: (a)
the 4-n-alkyl chain is replaced by an n-alkoxymethyl substituent,
1–3, or (b) the 4-n-alkyl chain is replaced by a methoxytriethy-
* Corresponding author. Tel.: +61 2 9385 4457; fax: +61 2 9385 6190.
leneglycolmethyl group, 4–6, and (c) there is
a 1-n-alkyl
E-mail address: r.read@unsw.edu.au (R.W. Read).
substituent in combination with a 4-perfluorohexylethoxymethyl
group, 7–11, or 4-perfluoroheptylmethoxymethyl group, 12–16,
respectively. In addition, a preliminary study towards a new class
of ether linked bis-1,2,3-triazoles [14] is described.
1
On leave from the Department of Chemistry, University of Central Florida,
Orlando, FL 32816-2366, USA.
2
On leave from Department of Chemistry, College of Science, Kerbala University,
Kerbala, Iraq.
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.07.002

D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
899
2. Results and discussion
under conventional conditions, by way of comparison, but the
expected triazoles 4–6 were isolated in only 52–58% yield. When
the last of these, reaction between fluorous azide 19 and propargyl
ether 21, was carried out under microwave irradiation conditions,
the product was obtained in much higher yield (80%) (Scheme 1).
This confirmed the benefits of microwave acceleration, which are
well-known, and demonstrated that they applied to this fluorous
setting.
Two synthetic pathways were taken to substances 1–16, and
the methods used reflect our modular approach to such fluorous
surfactants that are based on relatively simple heterocyclic core
molecules [24].
In the first approach, the heterocyclic portion was constructed
from fully substituted precursors. Known building blocks, fluorous
azides 17–19 [28,29], were made to react with each of propargyl
ethers 20 [30] and 21, under Cu(I)-catalysed Huisgen–Meldal 1,3-
dipolar cycloaddition conditions [31]. A number of different
protocols were tested. In our earlier studies [24], aqueous dimethyl
sulfoxide [31(d)], was adopted as solvent with good success. It was
recognised that dimethyl sulfoxide itself, in the absence of water,
was a useful dipolar aprotic solvent for the displacement of iodide
in the preparation of perfluoroalkylethyl azides. This prompted a
two-step, but one-pot procedure, to be examined in which the
azides 17–19 were prepared in situ. Such in situ generation of non-
fluorous azides followed by dipolar cycloaddition with copper-
ligated alkynes to generate 1,4-disubstituted triazoles has been
reported in various aqueous organic solvent combinations [32–34],
but in our case, to respect the hydrophobicity of the fluorous
substrates, neat dimethyl sulfoxide was used as solvent in both
steps, with no added water. In addition, each step in the overall
process using propargyl ether 20 was carried out under microwave
irradiation [35], while each step using propargyl ether 21 was
carried out under ‘conventional’ conditions, by regular heating. The
former reactions were complete within a total of 3 h while those
under conventional conditions required reaction times of 36 h. The
reactions all proceeded with excellent regioselectivity to afford the
desired 1,4-disubstituted derivatives 1–6 in acceptable to good
yields, with the highest derived from the microwave accelerated
protocol (Scheme 1). The fluorous azides 17–19 were also prepared
separately, purified and reacted directly with propargyl ether 21
The simpler ether derivatives 1–3 were higher melting than the
triethyleneglycol-substituted derivatives 4–6, while the latter
were noticeably more difficult to handle and purify.
Next, a series of n-alkyl azides, including benzyl azide, 22–26,
were made to react under the same 1,3-dipolar cycloaddition
conditions with each of fluorous propargyl ethers, 27 and 28.
Compounds 27 and 28 were readily prepared under phase transfer
conditions from the corresponding alcohol and propargyl bromide
[36]. In this series, the 1,3-dipolar cycloaddition reactions were
carried out under conventional conditions, and because the azides
22–26 were prepared from a variety of alkyl halides, they were pre-
prepared separately. Again, the reactions proceeded with virtually
perfect regioselectivity to yield the 1,2,3-triazoles 7–16 in good to
excellent yields. The compounds were isolated in some cases as oils
and waxes and in others crystalline materials. As expected, the more
highly fluorinated derivatives, 12–16, were higher melting than
their less fluorinated analogues (see Tables in Supplementary Data).
The influence of the compounds on surface tension of m-xylene
has been described in the accompanying paper [26], but, by and
large, these materials behaved consistently in reducing the surface
tension, although again, the 1-n-octyl derivatives showed some
deviation from the expected behaviour. Very significantly, it was
noted that the hydrophilic derivatives showed higher and more
consistent surface activity than the lipophilic analogues. This
difference in behaviour was consistent with similar findings for
perfluoroalkyl ether-substituted versus perfluoroalkyl-substituted
Scheme 1. Preparation of triazolyl ethers 1–16 and hydroxymethyltriazole 30 through Cu(I)-catalysed azide–alkyne dipolar cycloaddition.

900
D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
Scheme 2. Preparation of hydroxymethyltriazoles 30 and 37, triazolyl propargyl ethers 31 and 38, and di(triazolylmethyl) ethers 33–36 and 39.
benzenes [37]. An alternative approach to ether-substituted
triazoles involving functionalisation of preformed heterocycles
was therefore investigated and access to more elaborate fluorous
1,2,3-triazole derivatives was also explored.
thin films of neat liquid and in KBr disks for solids; measurements
are reported as wavenumbers in cmꢀ1. Routine 1H, 13C and 19F
NMR spectra were obtained on a Bruker DPX300F spectrometer.
Chemical shifts were recorded in parts per million (ppm) relative
to solvent nuclei as an internal reference. Mass spectra were
measured using the electrospray ionization (ESI) technique, at low
resolution on a Waters Micromass ZQ2000 LC–MS instrument by
direct injection and at high resolution using a Thermo LTQ Orbitrap
XL instrument. Samples were dissolved in MeOH. Microanalyses
were carried out at the Microanalytical Laboratory, Australian
National University. All chemicals were commercial reagent grade
unless otherwise specified.
There has been some interest in gemini fluorous surfactants,
such as bis-tetraalkylammonium salts [19], because they have
enhanced bioactivity and can form unique self assembled clusters.
The fluorous, ether-substituted triazoles have similar potential to
be fashioned into interesting gemini heterocycles through
synthesis of ether linked di-heterocycles. We wished to demon-
strate this concept in principle and have synthesised two pseudo
symmetrical and three unsymmetrical examples. Huisgen–Meldal
dipolar cycloaddition [32] between n-octyl azide 25 and propargyl
alcohol 29 proceeded well in aqueous tert-butanol (Scheme 1) and
the intermediate 4-hydroxymethyl-1-n-octyl-1,2,3-triazole 30
[35] was treated with propargyl bromide under phase transfer
conditions with sodium hydroxide as base (Scheme 2). Subsequent
reaction of the propargyl ether 31 with perfluorobutylethyl azide
17, perfluorohexylethyl azide 18, perfluorooctylethyl azide 19, and
perfluoroheptylmethyl azide 32, again under copper(I)-promoted
click conditions [31], gave the desired, new bis-1,2,3-triazoles 33–
36. Similarly, dipolar cycloaddition of n-nonyl azide 25 with
propargyl alcohol 29 yielded new 4-hydroxymethyl-1-n-nonyl-
1,2,3-triazole 37, which was subsequently transformed into its
propargyl ether 38. Treatment of propargyl ether 38 with
perfluorooctylethyl azide 19 under copper(I)-promoted conditions
proceeded without incident to bis-1,2,3-triazole 39.
3.2. General method for preparation of alkynyl ethers 20 and 21
A dry flask was charged with THF (15 mL), NaOH pellets (2.40 g,
60 mmol), and n-octanol or triethyleneglycol monomethyl ether
(15 mmol). The flask was immersed in an ice-bath and the contents
stirred for 10 min. before propargyl bromide (2.51 mL, 22.5 mmol)
was added dropwise. The reaction mixture was then allowed to stir
for 24 h, gradually warming to r.t. The reaction mixture was poured
into Et2O (20 mL) and water (50 mL) and the layers were separated.
The aqueous layer was further extracted with Et2O (2 ꢁ 20 mL),
and the combined organic extracts were washed with 10% aq. HCl,
followed by sat. NaHCO3 solution and brine, and then dried over
MgSO4. Column chromatography (silica gel, Et2O/light petroleum,
10:90) followed by Kulgelrohr distillation gave the desired
products.
The structures of triazoles 33–36 contain the same n-octyl
substituent in one triazole ring but (a) increasing fluorous
substituents of increasing chain length (33–35), and (b) fluorous
chains of equal length and increasing fluorine content (34 and 36),
in the second ring. Meanwhile, bis-triazoles 35 and 39 bear
identical N-perfluorooctylethyl substituents in one heterocyclic
ring but non-fluorous n-alkyl substituents of increasing chain
length in the other. Together, this collection of new compounds
3.2.1. 1-(Prop-2-ynyloxy)octane 20
n-Octanol (1.95 g) gave 1-(prop-2-ynyloxy)octane 20 as a
colourless oil (2.39 g, 95%) bp 79–81 8C/0.1 mmHg (lit. [30]: bp
80 8C (oven)/0.13 mmHg). IR (neat): 3583, 3312, 2927, 2856, 2117,
1467, 1443, 1378, 1357, 1269, 1104, 1026, 945, 917, 722, 665, 622,
422 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d: 0.87 (t, J 6.6 Hz, 3H,
comprises
structural variations for further study.
The scope of these functionalised fluorous molecules for self-
assembly, drug transport, and additional functionalisation, will be
investigated in future.
a
valuable small library with highly systematic
CH3CH2), 1.26 (m, 8H, (CH2)4CH3), 1.33 (m, 2H, CH2CH2CH2O), 1.58
(m, 2H, CH2CH2O), 2.40 (t, J 2.4 Hz, 1H, OCH2CCH), 3.49 (t, J 6.7 Hz,
2H, CH2CH2O), 4.12 (d, J 2.4 Hz, 2H, OCH2CCH). 13C NMR (75 MHz,
CDCl3) d: 14.0 (CH3), 22.5 (CH2CH3), 26.0 (CH2), 29.1 (CH2), 29.4
(CH2), 29.6 (CH2), 31.7 (CH2CH2O), 57.9 (OCH2CCH), 70.2
(CH2OCH2CCH), 73.9 (OCH2CCH), 80.0 (OCH2CCH). HR-MS (ESI)
Calcd. for [C11H20O+H]+: m/z 169.1587. Found: m/z 169.1582. Anal.
Calcd. for C11H20Oꢂ0.33H2O: C, 75.83; H, 11.96%. Found: C, 75.73;
H, 12.11%.
3. Experimental
3.1. General
Melting points were determined using a Ko¨fler hotstage
melting point apparatus and are uncorrected. Infrared spectra
were recorded on a Nicolet Avatar 320 FT-IR spectrophotometer as
3.2.2. 3-(2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)prop-1-yne 21
Triethyleneglycol monomethyl ether (2.46 g) gave 3-(2-(2-(2-
methoxyethoxy)ethoxy)ethoxy)prop-1-yne 21 as a colourless oil

D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
901
(2.48 g, 82%) bp 130–133 8C (oven)/0.1 mmHg. IR (neat): 3582,
3428, 3278, 2880, 2114, 1724, 1650, 1454, 1352, 1287, 1247, 1197,
1104, 1032, 935, 887, 850, 666 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d:
2.41 (t, J 2.4 Hz, 1H, OCH2CCH), 3.36 (s, 3H, OCH3), 3.54 (m, 2H,
CH2CH2OCH3), 3.62 (m, 2H, OCH2CH2OCH3), 3.65 (m, 4H,
2 ꢁ OCH2CH2), 3.66 (m, 2H, CH2OCH2CCH), 3.67 (m, 2H, OCH2-
CH2OCH2CCH), 4.18 (d, J 2.4 Hz, 2H, OCH2CCH). 13C NMR (75 MHz,
(CH2)4CH3), 1.31 (m, 2H, OCH2CH2CH2), 1.58 (tt, J 7.0, 6.6 Hz, 2H,
3
3
OCH2CH2), 2.80 (tt, JH–F 18.0, JH–H 7.4 Hz, 2H, CH2CF2), 3.50 (t, J
6.6 Hz, 2H, OCH2CH2), 4.62 (s, 2H, 4-CH2O), 4.67 (dd, J 7.5, 7.4 Hz,
2H, N1CH2CH2CF2), 7.61 (s, 1H, H5). 13C NMR (100 MHz, CDCl3)
d:
14.2 (CH3), 22.8 (CH2CH3), 26.2 (CH2), 29.4 (CH2), 29.5 (CH2), 29.7
2
(CH2), 31.8 (t, JC–F 21.7 Hz, N1CH2CH2CF2), 31.9 (OCH2CH2), 42.2
3
(br t, JC–F 4.9 Hz, N1CH2CH2CF2), 64.3 (4-CH2O), 71.1 (OCH2CH2),
CDCl3)
d
: 58.3 (OCH2CCH), 58.9 (OCH3), 69.0 (CH2OCH2CCH), 70.3
123.1 (C5-H), 146.0 (C4). MS (ESI) m/z: 596.00 ([M+K]+, 3%), 581.03
([M+H+Na]+, 25), 580.03 ([M+Na]+, 100), 558.04 ([M+H]+, 14). Anal.
Calcd. for C19H24F13N3O requires: C, 40.94; H, 4.34; N, 7.54%.
Found: C, 40.71; H, 4.46; N, 7.77%.
(OCH2CH2), 70.4 (OCH2CH2), 70.5 (2 ꢁ OCH2CH2), 71.8 (CH2OCH3),
74.4 (OCH2CCH), 79.5 (OCH2CCH). MS (ESI) m/z: 226.17
([M+H+Na]+, 10%), 225.16 ([M+Na]+, 100). Anal. Calcd. for
C10H18O4 requires C, 59.39; H, 8.97%. Found: C, 59.24; H, 9.28%.
3.3.3. 4-((Octyloxy)methyl)-1-(2-(perfluorooctyl)ethyl)-1H-1,2,3-
triazole 3
3.3. General method for the microwave accelerated reactions of
propargyl ether 20 with in situ prepared perfluoroalkylethyl azides
17–19
Perfluorooctylethyl iodide (1.722 g, 3.0 mmol) was converted to
its azide 19 through microwave irradiation at 85 8C for 1 h, then
treated with propargyl ether 20 (0.505 g, 3.0 mmol) at 98 8C for
2.5 h to afford 4-((octyloxy)methyl)-1-(2-(perfluorooctyl)ethyl)-1H-
1,2,3-triazole 3 as white needles (1.63 g, 83%) mp 80–82 8C (Et2O-
light petroleum). IR (KBr): 3646, 3410, 2933, 1443, 1359, 1204,
1148, 1116, 1063, 1032, 983, 957, 921, 746, 706, 660, 585, 557,
Perfluoroalkylethyl iodide (1.0 mol equiv.) (3–4 mmol) and
NaN3 (1.2 mol equiv.) were added to dry DMSO (2 mL) in a 10 mL
CEM microwave glass reactor tube, a magnetic stirring bead added
and the system sealed. The tube was subjected to stirring and
microwave irradiation at 250 W and 65 8C for 1 h then immedi-
ately cooled to r.t. The tube was opened and n-octyl propargyl
ether 41 (1.0 mol equiv.) added, followed by sodium ascorbate
(0.1 mol equiv.) and CuSO4ꢂ5H2O (0.05 mol equiv.) and additional
DMSO (1 mL). The tube was again sealed and again subjected to
stirring and microwave irradiation at elevated temperature. At the
conclusion of the reaction, the tube was cooled, opened, and the
contents diluted with water (25 mL). The product was then
extracted into Et2O (3 ꢁ 20 mL), and the combined extracts
washed in turn with brine (2 ꢁ 10 mL), H2O (2 ꢁ 10 mL) and again
brine (10 mL), and then dried and evaporated. The residue was
chromatographed on silica gel and the product eluted with a
gradient of Et2O/light petroleum.
518 cmꢀ1 1H NMR (400 MHz, CDCl3)
. d: 0.86 (t, J 6.8 Hz, 3H, CH3),
1.24 (m, 8H, (CH2)4CH3), 1.31 (m, 2H, OCH2CH2CH2), 1.58 (tt, J 7.1,
6.8 Hz, 2H, OCH2CH2), 2.81 (tt, 3JH–F 18.0, 3JH–H 7.5 Hz, 2H, CH2CF2),
3.50 (t, J 6.7 Hz, 2H, OCH2CH2), 4.62 (s, 2H, 4-CH2O), 4.68 (dd, J 7.5,
7.3 Hz, 2H, N1CH2CH2CF2), 7.61 (s, 1H, H5). 13C NMR (100 MHz,
CDCl3) d: 14.2 (CH3), 22.8 (CH2CH3), 26.2 (CH2), 29.4 (CH2), 29.5
2
(CH2), 29.7 (CH2), 31.86 (t, JC–F 21.8 Hz, N1CH2CH2CF2), 31.93
3
(OCH2CH2), 42.4 (br t, JC–F 4.6 Hz, N1CH2CH2CF2), 64.3 (4-CH2O),
71.1 (OCH2CH2), 123.1 (C5-H), 146.1 (C4). MS (ESI) m/z: 680.93
([M+Na]+, 23%), 679.93 ([M–H+Na]+, 100). Anal. Calcd. for
C21H24F17N3O requires: C, 38.37; H, 3.68; N, 6.39%. Found: C,
38.44; H, 3.76; N, 6.46%.
3.4. General method for the preparation of 4-((2-(2-(2-
methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-perfluoroalkylethyl)-
1H-1,2,3-triazoles 4–6 by conventional, thermal reactions of
propargyl ether 21 with in situ prepared perfluoroalkylethyl azides
17–19
3.3.1. 4-((Octyloxy)methyl)-1-(2-(perfluorobutyl)ethyl)-1H-1,2,3-
triazole 1
Perfluorobutylethyl iodide (1.496 g, 4.0 mmol) was converted
to its azide 17 at 75 8C for 1 h and then treated with propargyl ether
20 (0.673 g, 4.0 mmol) at 95 8C for 2 h to afford 4-((octyloxy)-
methyl)-1-(2-(perfluorobutyl)ethyl)-1H-1,2,3-triazole
1
as white
Perfluoroalkylethyl iodide (1.0 mol equiv.) (3–5 mmol) and
NaN3 (1.0–1.5 mol equiv.) were added to dry DMSO (4 mL), a
magnetic stirring bead added, and the mixture stirred under argon
in a bath at 65 8C for 24 h then cooled to r.t. The methoxytriethy-
lenoxy propargyl ether 21 (1.0 mol equiv.) added, followed by
sodium ascorbate (0.1 mol equiv.) and CuSO4ꢂ5H2O (0.05 mol
equiv.), and additional DMSO (2 mL). The mixture was again stirred
under argon at elevated temperature for 48 h. The contents were
cooled and diluted with water (50 mL). The product was then
extracted into Et2O (3 ꢁ 20 mL), and the combined extracts
washed in turn with brine (2 ꢁ 10 mL), H2O (2 ꢁ 10 mL) and again
brine (10 mL), then dried and evaporated. The residue was
chromatographed on silica gel and the product eluted with a
gradient of Et2O/light petroleum and distilled or characterized
directly as an oil.
needles (1.59 g, 87%) mp 40–42 8C (Et2O-light petroleum). IR
(KBr): 3500, 2924, 1467, 1359, 1225, 1134, 1053, 1018, 988, 881,
859, 771, 738, 700, 668, 646, 596, 531 cmꢀ1 1H NMR (400 MHz,
.
CDCl3) d: 0.86 (t, J 7.0 Hz, 3H, CH3), 1.28 (m, 8H, (CH2)4CH3), 1.31
(m, 2H, OCH2CH2CH2), 1.58 (tt, J 7.4, 6.7 Hz, 2H, OCH2CH2), 2.81 (tt,
3JH–F 18.0, 3JH–H 7.4 Hz, 2H, CH2CF2), 3.50 (t, J 6.7 Hz, 2H, OCH2CH2),
4.61 (s, 2H, 4-CH2O), 4.66 (dd, J 7.6, 7.3 Hz, 2H, N1CH2CH2CF2), 7.58
(s, 1H, H5). 13C NMR (100 MHz, CDCl3)
d: 14.2 (CH3), 22.8 (CH2CH3),
26.2 (CH2), 29.4 (CH2), 29.5 (CH2), 29.8 (CH2), 31.90 (t, 2JC–F 21.7 Hz,
3
N1CH2CH2CF2), 31.93 (OCH2CH2), 42.4 (br t, JC–F 5.2 Hz,
N1CH2CH2CF2), 64.4 (4-CH2O), 71.2 (OCH2CH2), 122.9 (C5),
146.2 (C4). MS (ESI) m/z: 481.07 ([M+H+Na]+, 31%), 480.13
([M+Na]+, 100). Anal. Calcd. for C17H24F9N3O requires: C, 44.64;
H, 5.29; N, 9.19%. Found: C, 44.76; H, 5.02; N, 9.33%.
3.3.2. 4-((Octyloxy)methyl)-1-(2-(perfluorohexyl)ethyl)-1H-1,2,3-
triazole 2
3.4.1. 4-((2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-
perfluorobutylethyl)-1H-1,2,3-triazole 4
Perfluorohexylethyl iodide (1.422 g, 3.0 mmol) was converted
to its azide 18 through treatment at 75 8C for 1 h, then treated with
propargyl ether 20 (0.505 g, 3.0 mmol) at 95 8C for 2 h to afford 4-
Perfluorobutylethyl iodide (1.87 g, 5.0 mmol) was treated with
NaN3 (0.49 g, 7.5 mmol) at 65 8C for 24 h to generate azide 17,
which was then treated with propargyl ether 21 (1.02 g, 5.0 mmol)
at 90 8C for 48 h to give 4-((2-(2-(2-methoxyethoxy)ethoxy)ethox-
y)methyl)-1-(2-perfluorobutylethyl)-1H-1,2,3-triazole 4 as pale yel-
low wax (1.62 g, 66%) bp 223–228 8C (oven)/0.1 mmHg. IR (neat):
3139, 2882, 2357, 2248, 1714, 1664, 1646, 1455, 1403, 1352, 1223,
((octyloxy)methyl)-1-(2-(perfluorohexyl)ethyl)-1H-1,2,3-triazole
2
as white needles (1.35 g, 81%) mp 52–54 8C (Et2O-light petroleum).
IR (KBr): 3521, 3101, 2935, 1468, 1240, 1196, 1138, 1118, 1095,
1078, 1054, 998, 982, 845, 786, 768 725, 712, 680, 642, 565 cmꢀ1
.
1H NMR (400 MHz, CDCl3)
d
: 0.85 (t, J 6.8 Hz, 3H, CH3), 1.24 (m, 8H,
1135, 1049, 990, 928, 881, 858, 832, 748, 710, 666 cmꢀ1 1H NMR
.

902
D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
3
3
(300 MHz, CDCl3)
d
: 2.78 (tt, JH–F 18.1, JH–H 7.2 Hz, 2H, CH2CF2),
(3 mmol). The flask was immersed in an ice-bath and the contents
stirred for 10 min. Propargyl bromide (0.54 g, 4.5 mmol) was
added dropwise and the reaction mixture stirred and gradually
allowed to warm to r.t. over 24 h. The reaction mixture was poured
into Et2O (20 mL) and water (50 mL), the layers separated and the
aqueous layer extracted with more Et2O (3 ꢁ 20 mL). The
combined organic extracts were washed with 10% HCl soln.
followed by sat. aq. NaHCO3 and brine, and then dried over Na2SO4.
Column chromatography (silica gel, Et2O/LP, 10:90) followed by
Kulgelrohr distillation gave the desired products.
3.32 (s, 3H, OCH3), 3.50 (t, J 4.4 Hz, 2H, CH2OCH3), 3.55–3.67 (m,
10H, 5 ꢁ OCH2CH2), 4.64 (partially obscured dd, J 7.2, ca. 6.4 Hz,
2H, N1CH2CH2CF2), 4.65 (s, 2H, 4-CH2O), 7.65 (s, 1H, H5). 13C NMR
(75 MHz, CDCl3)
ca. 4 Hz, N1CH2CH2CF2), 58.8 (OCH3), 64.5 (4-CH2O), 69.7 (4-
d
: 31.6 (t, 2JC–F 21.7 Hz, N1CH2CH2CF2), 42.1 (t, 3JC–
F
CH2OCH2), 70.35 (OCH2CH2), 70.40 (OCH2CH2), 70.42 (OCH2CH2),
70.47 (OCH2CH2), 71.8 (CH2OCH3), 123.0 (C5-H), 145.6 (C4). MS
(ESI) m/z: 515.29 ([M+H+Na]+, 23%), 514.22 ([M+Na]+, 100), 492.10
([M+H]+, 20). HR-MS (ESI) Anal. Calcd. for [C16H22N3O4F9+Na+H]+
m/z: 515.1443. Found: m/z 515.1390 (19%); Anal. Calcd. for
[C16H22N3O4F9+Na]+ m/z 514.1365. Found: m/z 514.1361 (100);
Anal. Calcd. for [C16H22N3O4F9+H]+ m/z 492.1545. Found: m/z
492.1549 (15).
3.5.1. 3-((2-Perfluorohexyl)ethoxy)prop-1-yne 27
Perfluorohexylethanol (1.09 g) gave 3-((2-perfluorohexyl)ethox-
y)prop-1-yne 27 as a colourless oil (0.96 g, 80%) bp 125–128 8C
(oven)/0.1 mmHg. IR (neat): 3850, 3608, 3683, 3317, 2960, 2898,
3.4.2. 4-((2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-
perfluorohexylethyl)-1H-1,2,3-triazole 5
2859, 2360, 2342, 2122, 1362, 1240, 1146, 1010, 913, 811, 708,
3
698, 653 cmꢀ1
.
1H NMR (300 MHz, CDCl3)
d
: 2.43 (ttt, JH–F 18.6,
4
Perfluorohexylethyl iodide (2.37 g, 5.0 mmol) was treated
with NaN3 (0.48 g, 7.5 mmol) at 65 8C for 24 h to generate azide
18, which was then treated with propargyl ether 21 (1.03 g,
5.1 mmol) in a bath at 100 8C for 48 h to give 4-((2-(2-(2-
methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-perfluorohexylethyl)-
1H-1,2,3-triazole 5 as a pale yellow wax (2.09 g, 71%). IR (neat):
3138, 2879, 1731, 1646, 1456, 1402, 1366, 1351, 1319, 1240,
1206, 1145, 1122, 1050, 989, 949, 850, 810, 746, 736, 708, 699,
3JH–H 6.8, JH–F 1.4 Hz, 2H, OCH2CH2CF2), 2.46 (t, J 2.4 Hz, 1H,
OCH2CCH), 3.82 (t, J 6.8 Hz, 2H, OCH2CH2CF2), 4.18 (d, J 2.4 Hz, 2H,
2
OCH2CCH). 13C NMR (75 MHz, CDCl3)
d
: 31.3 (t, JC–F 21.5 Hz,
OCH2CH2CF2), 58.3 (OCH2CCH), 61.6 (t, 3JC–F ca. 5 Hz, OCH2CH2CF2),
74.9 (OCH2CCH), 78.8 (OCH2CCH). MS (ESI) m/z: 425.14 ([M+Na]+).
Anal. Calcd. for C11H7F13O requires C, 32.85; H, 1.75%. Found: C,
32.53; H, 1.68%.
3
3
666 cmꢀ1
.
1H NMR (300 MHz, CDCl3)
d
: 2.82 (tt, JH–F 18.5, JH–H
3.5.2. 3-((2-Perfluoroheptyl)methoxy)prop-1-yne 28
7.2 Hz, 2H, CH2CF2), 3.37 (s, 3H, OCH3), 3.55 (t, J 4.7 Hz, 2H,
CH2OCH3), 3.60–3.80 (m, 10H, 5 ꢁ OCH2CH2), 4.68 (dd, J 7.5,
7.5 Hz, 2H, N1CH2CH2CF2), 4.71 (s, 2H, 4-CH2O), 7.71 (s, 1H, H5).
Perfluoroheptylmethanol (1.20 g) gave 3-(perfluoroheptyl-
methoxy)prop-1-yne 28 as a colourless oil (1.12 g, 85%) b.p. 130–
132 8C (oven)/0.1 mmHg. IR (neat): 3850, 3583, 3317, 2924, 2360,
2342, 2126, 1690, 1464, 1448, 1362, 1328, 1213, 1150, 1090, 1023,
13C NMR (75 MHz, CDCl3) : 31.7 (t, 2JC–F 21.7 Hz, N1CH2CH2CF2),
d
42.1 (br, N1CH2CH2CF2), 58.8 (OCH3), 64.5 (4-CH2O), 69.7 (4-
CH2OCH2), 70.35 (OCH2CH2), 70.40 (OCH2CH2), 70.42 (OCH2CH2),
70.48 (OCH2CH2), 71.8 (CH2OCH3), 123.1 (C5-H), 145.7 (C4). MS
(ESI) m/z: 615.36 ([M+H+Na]+, 8%), 614.30 ([M+Na]+, 100). HR-MS
(ESI) Anal. Calcd. for [C18H22N3O4F13+Na+H]+ m/z: 615.1379.
Found: m/z 615.1337 (21%); Anal. Calcd. for [C18H22N3O4F13+Na]+
requires m/z 614.1301. Found: m/z 614.1309 (100). Anal. Calcd.
for [C18H22N3O4F13+H]+ requires m/z 592.1481. Found: m/z
592.1500 (22).
963, 884, 808, 722, 702, 660 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d:
2.54 (t, J 2.4 Hz, 1H, OCH2CCH), 4.05 (tt, 3JH–F 13.8, 4JH–F 1.5 Hz, 2H,
OCH2CF2), 4.32 (d, J 2.4 Hz, 2H, OCH2CCH). 13C NMR (75 MHz,
CDCl3)
d: 59.3 (OCH2CCH), 65.7 (t, J 25.5 Hz, OCH2CF2), 76.2
(OCH2CCH), 77.4 (OCH2CCH). MS (ESI) m/z: 439.21([M+1]+). Anal.
Calcd. for C11H5F15O requires C, 30.16; H, 1.15%. Found: C, 30.32; H,
1.08%.
3.6. General procedure for the preparation of triazoles 7–16
3.4.3. 4-((2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-
perfluorooctylethyl)-1H-1,2,3-triazole 6
Propargyl ether (alkyne) (1 mmol) and alkyl azide (2 mmol)
were added to a suspension of sodium ascorbate (0.0198 g,
0.10 mmol) and CuSO4ꢂ5H2O (0.0125 g, 0.05 mmol) in (CH3)2SO
(4 mL). The mixture was stirred and heated in a bath to 60 8C for
48 h. The reaction mixture was diluted with water (20 mL),
extracted with Et2O (3 ꢁ 15 mL). The combined organic layers
were washed with brine (2 ꢁ 10 mL), dried over Na2SO4, and
evaporated to dryness under reduced pressure. The residue was
flash chromatographed (silica gel, Et2O/LP 10:90 to 20:80) and
the main fraction recrystallized from light petroleum where
appropriate.
Perfluorooctylethyl iodide (1.72 g, 3.0 mmol) was treated with
NaN3 (0.23 g, 3.0 mmol) in a bath at 70 8C for 24 h to generate azide
19, which was then treated with propargyl ether 21 (0.61 g,
3.0 mmol) in a bath at 110 8C for 48 h to give 4-((2-(2-(2-
methoxyethoxy)ethoxy)ethoxy)methyl)-1-(2-perfluorooctylethyl)-
1H-1,2,3-triazole 6 as a white powder (1.53 g, 79%) mp 47–49 8C
(Et2O/light petroleum). IR (KBr): 3126, 2875, 2368, 1715, 1557,
1539, 1455, 1401, 1372, 1338, 1201, 1151, 1115, 1053, 989, 958,
851, 706, 660 cmꢀ1
.
1H NMR (300 MHz, CDCl3)
d
: 2.82 (tt, JH–F
3
18.5, 3JH–H 7.5 Hz, 2H, CH2CF2), 3.36 (s, 3H, OCH3), 3.55 (t, J 4.2 Hz,
2H, CH2OCH3), 3.60–3.75 (m, 10H, 5 ꢁ OCH2CH2), 4.68 (dd, J 7.5,
3.6.1. Preparations involving 3-(2-perfluorohexylethoxy)propyne 27
Propargyl ether 27 (0.40 g, 1.00 mmol) was made to react with
the following sections.
7.5 Hz, 2H, N1CH2CH2CF2), 4.71 (s, 2H, 4-CH2O), 7.70 (s, 1H, H5).
13C NMR (75 MHz, CDCl3)
2
d
: 31.6 (t, JC–F 21.7 Hz, N1CH2CH2CF2),
42.1 (br, N1CH2CH2CF2), 58.7 (OCH3), 64.4 (4-CH2O), 69.6 (4-
CH2OCH2), 70.30 (OCH2CH2), 70.36 (OCH2CH2), 70.38 (OCH2CH2),
70.43 (OCH2CH2), 71.7 (CH2OCH3), 123.2 (C5-H), 145.5 (C4). MS
(ESI) m/z: 715.36 ([M+H+Na]+, 14%), 714.23 ([M+Na]+, 100). Anal.
Calcd. for C20H22F17N3O4 requires: C, 34.74; H, 3.21; N, 6.08%.
Found: C, 34.63; H, 2.97; N, 5.90%.
3.6.1.1. 1-n-Butyl-4-(2-perfluorohexylethoxy)methyl-1H-1,2,3-tria-
zole 7. n-Butyl azide (0.20 g, 2.02 mmol) to give 1-n-butyl-4-(2-
perfluorohexylethoxy)methyl-1H-1,2,3-triazole 7 as a pale yellow oil
(0.32 g, 64%). IR (neat): 3850, 3583, 3444, 3137, 2965, 2939, 2879,
2359, 2342, 1643, 1468, 1441, 1366, 1318, 1240, 1206, 1146, 1124,
1049, 1023, 951, 810, 708, 698, 652 cmꢀ1
.
1H NMR (300 MHz,
3.5. General method for the preparation of alkynyl ethers 27 and 28
CDCl3) : 0.95 (t, J 7.5 Hz, 3H, CH3), 1.36 (qt, J 7.5, 7.2 Hz, 2H,
d
CH2CH3), 1.89 (tt, J 7.5, 7.2 Hz, 2H, N1CH2CH2), 2.42 (tt, 3JH–F 18.5,
3JH–H 6.4 Hz, 2H, OCH2CH2CF2), 3.82 (t, J 6.4 Hz, 2H, OCH2CH2CF2),
4.36 (t, J 7.5 Hz, 2H, N1CH2CH2), 4.68 (s, 2H, 4-CH2O), 7.52 (s, 1H,
A dry flask was charged with THF (9 mL), NaOH pellets (0.48 g,
12 mmol), and perfluorohexylethanol or perfluoroheptylmethanol

D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
903
3
H5). 13C NMR (75 MHz, CDCl3)
d
: 13.2 (CH3), 19.6 (CH2CH3), 31.4 (t,
3JH–F 18.5, JH–H 6.8 Hz, 2H, OCH2CH2CF2), 3.80 (t, J 6.8 Hz, 2H,
OCH2CH2CF2), 4.64 (s, 2H, 4-CH2O), 5.53 (s, 2H, N1CH2C6H5), 7.28
(m, 2H, N1CH2C6H5-ortho), 7.36 (m, 1H, N1CH2C6H5-para), 7.37 (m,
2JC–F 22.4 Hz, OCH2CH2CF2), 32.1 (N1CH2CH2), 50.0 (N1CH2CH2),
62.1 (br, OCH2CH2CF2), 64.5 (4-CH2O), 122.2 (C5-H), 144.4 (C4). MS
(ESI) m/z: 540.33 ([M+K]+), 524.31 ([M+Na]+). Anal. Calcd. for
2H, N1CH2C6H5-meta), 7.44 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d
:
2
C15H16F13N3O requires: C, 35.94; H, 3.22; N, 8.38%. Found: C, 35.95;
31.4 (t, JC–F 20.9 Hz, OCH2CH2CF2), 54.2 (N1CH2C6H5), 62.2 (t, J
4.3 Hz, OCH2CH2CF2), 64.5 (4-CH2O), 122.3 (C5-H), 128.0
(N1CH2C6H5-ortho), 128.7 (N1CH2C6H5-para), 129.0 (N1CH2C6H5-
meta), 134.3 (N1CH2C6H5-ipso), 144.9 (C4). MS (ESI) m/z: 558.33
([M+Na]+, 100%). Anal. Calcd. for C18H14F13N3O requires: C, 40.39;
H, 2.64; N, 7.85%. Found: C, 40.21; H, 2.68; N, 7.76%.
H, 3.33; N, 8.12%.
3.6.1.2. 1-n-Hexyl-4-(2-perfluorohexylethoxy)methyl-1H-1,2,3-tria-
zole 8. n-Hexyl azide (0.25 g, 1.97 mmol) to give 1-n-hexyl-4-(2-
perfluorohexylethoxy)methyl-1H-1,2,3-triazole 8 as pale yellow wax
(0.51 g, 97%) mp 31–32 8C. IR (KBr): 3130, 2960, 2935, 2862, 2362,
1466, 1445, 1368, 1320, 1238, 1208, 1192, 1145, 1124, 1107, 1091,
3.6.2. Preparations involving 3-(perfluoroheptylmethoxy)propyne 28
Propargyl ether 28 (0.44 g, 1.00 mmol) was made to react with
the following sections.
1057, 1008, 951, 844, 708, 700, 653 cmꢀ1
.
1H NMR (300 MHz,
CDCl3) : 0.88 (t, J 6.8 Hz, 3H, CH3), 1.27 (m, 2H, CH2CH3), 1.31 (m,
d
4H, N1CH2CH2(CH2)2), 1.90 (tt, J 6.8, 6.8 Hz, 2H, N1CH2CH2), 2.42
(tt, 3JH–F 18.8, 3JH–H 6.8 Hz, 2H, OCH2CH2CF2), 3.82 (t, J 6.8 Hz, 2H,
OCH2CH2CF2), 4.34 (t, J 7.5 Hz, 2H, N1CH2CH2), 4.67 (s, 2H, 4-
3.6.2.1. 1-n-Butyl-4-(perfluoroheptylmethoxy)methyl-1H-1,2,3-tria-
zole 12. n-Butyl azide (0.20 g, 2.02 mmol) to give 1-n-butyl-4-
(perfluoroheptylmethoxy)methyl-1H-1,2,3-triazole 12 as pale yellow
oil (0.45 g, 84%). IR (neat): 3850, 3685, 3583, 3138, 2965, 2940,
2880, 1642, 1552, 1468, 1366, 1327, 1241, 1210, 1150, 1051, 1030,
CH2O), 7.51 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d: 13.7 (CH3),
22.3 (CH2CH3), 26.0 (CH2), 30.1 (CH2), 31.0 (N1CH2CH2), 31.4 (t, 2JC–
F 21.7 Hz, OCH2CH2CF2), 50.3 (N1CH2CH2), 62.1 (br, OCH2CH2CF2),
64.5 (4-CH2O), 122.2 (C5-H), 144.4 (C4). MS (ESI), m/z: 553.48
([M+H+Na]+, 30%), 552.53 ([M+Na]+, 100). Anal. Calcd. for
992, 953, 808, 711, 698, 658 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d:
0.96 (t, J 7.5 Hz, 3H, CH3), 1.36 (qt, J 7.5, 7.2 Hz, 2H, CH2CH3), 1.89
3
C17H20F13N3O requires: C, 38.57; H, 3.81; N, 7.94%. Found: C,
(tt, J 7.3, 7.2 Hz, 2H, N1CH2CH2), 4.03 (t, JH–F 13.9 Hz, 2H,
38.95; H, 3.83; N, 7.72%.
OCH2CF2), 4.37 (t, J 7.3 Hz, 2H, N1CH2CH2), 4.80 (s, 2H, 4-CH2O),
7.56 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d: 13.1 (CH3), 19.5
3.6.1.3. 1-n-Octyl-4-(2-perfluorohexylethoxy)methyl-1H-1,2,3-tria-
zole 9. n-Octyl azide (0.31 g, 2.00 mmol) to give 1-n-octyl-4-(2-
perfluorohexylethoxy)methyl)-1H-1,2,3-triazole 9 as white powder
(0.50 g, 90%) mp 34–35 8C. IR (KBr): 3132, 2958, 2928, 2856, 2360,
1542, 1466, 1368, 1322, 1237, 1192, 1144, 1124, 1109, 1092, 1057,
1006, 951, 835, 789, 731, 702, 654 cmꢀ1. 1H NMR (300 MHz, CDCl3)
(CH2CH3), 32.1 (N1CH2CH2), 50.0 (N1CH2CH2), 65.6 (4-CH2O), 66.7
(t, 2JC–F 25.3 Hz, OCH2CF2), 122.5 (C5-H), 143.4 (C4). MS (ESI) m/z:
560.45 ([M+Na]+, 100%). Anal. Calcd. for C15H14F15N3O requires: C,
33.53; H, 2.63; N, 7.82%. Found: C, 33.82; H, 2.66; N, 7.53%.
3.6.2.2. 1-n-Hexyl-4-(perfluoroheptylmethoxy)methyl-1H-1,2,3-tria-
d: 0.87 (t, J 6.8 Hz, 3H, CH3), 1.26 (m, 6H, (CH2)3CH3), 1.32 (m, 4H,
zole 13. n-Hexyl azide (0.25 g, 1.97 mmol) to give 1-n-hexyl-4-
N1CH2CH2(CH2)2), 1.90 (tt, J 7.2, 6.8 Hz, 2H, N1CH2CH2), 2.42 (tt,
(perfluoroheptylmethoxy)methyl-1H-1,2,3-triazole 13 as a pale
yellow wax (0.50 g, 88%) mp 29–31 8C. IR (neat): 3616, 3132,
3
3JH–F 18.8, JH–H 6.8 Hz, 2H, OCH2CH2CF2), 3.82 (t, J 6.8 Hz, 2H,
OCH2CH2CF2), 4.34 (t, J 7.5 Hz, 2H, N1CH2CH2), 4.67 (s, 2H, 4-CH2O),
2958, 2932, 2862, 2360, 1563, 1468, 1369, 1329, 1207, 1147, 1058,
7.51 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d
: 13.8 (CH3), 22.4
1028, 992, 956, 808, 701, 659 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d:
2
(CH2CH3), 26.3 (CH2), 28.8 (CH2), 30.2 (CH2), 31.4 (t, JC–F 21.3 Hz,
OCH2CH2CF2), 31.7 (N1CH2CH2), 50.3 (N1CH2CH2), 62.1 (t, J 4.3 Hz,
OCH2CH2CF2), 64.5 (4-CH2O), 122.2 (C5-H), 144.4 (C4). MS (ESI) m/z:
580.59 ([M+Na]+, 100%). Anal. Calcd. for C19H24F13N3O requires: C,
40.94; H, 4.59; N, 7.54%. Found: C, 41.25; H, 4.53; N, 7.29%.
0.88 (t, J 6.8 Hz, 3H, CH3), 1.20–1.40 (m, 6H, (CH2)3CH3), 1.91 (tt, J
3
7.2, 7.2 Hz, 2H, N1CH2CH2), 4.02 (t, JH–F 13.6 Hz, 2H, OCH2CF2),
4.36 (t, J 7.2 Hz, 2H, N1CH2CH2), 4.80 (s, 2H, 4-CH2O), 7.55 (s, 1H,
H5). 13C NMR (75 MHz, CDCl3)
d: 13.6 (CH3), 22.2 (CH2CH3), 26.0
(CH2), 30.1 (CH2), 30.9 (N1CH2CH2), 50.4 (N1CH2CH2), 65.6 (4-
CH2O), 66.7 (t, 2JC–F 25.3 Hz, OCH2CF2), 122.4 (C5-H), 143.5 (C4). MS
(ESI) m/z: 589.52 ([M+H+Na]+, 4%), 588.58 ([M+Na]+, 100). Anal.
Calcd. for C17H18F15N3O requires: C, 36.12; H, 3.21; N, 7.43%.
Found: C, 36.35; H, 3.36; N, 7.37%.
3.6.1.4. 1-n-Nonyl-4-(2-perfluorohexylethoxy)methyl-1H-1,2,3-tria-
zole 10. n-Nonyl azide (0.58 g, 3.43 mmol) to give 1-n-nonyl-4-(2-
perfluorohexylethoxy)methyl)-1H-1,2,3-triazole 10 as white powder
(0.47 g, 82%) mp 41–43 8C. IR (KBr): 3842, 3133, 2957, 2925, 2851,
2360, 2341, 1547, 1467, 1368, 1322, 1236, 1207, 1191, 1144, 1124,
1109, 1056, 1028, 843, 790, 732, 702, 654 cmꢀ1. 1H NMR (300 MHz,
3.6.2.3. 1-n-Octyl-4-(perfluoroheptylmethoxy)methyl-1H-1,2,3-tria-
zole 14. n-Octyl azide (0.31 g, 2.00 mmol) to give 1-n-octyl-4-
(perfluoroheptylmethoxy)methyl-1H-1,2,3-triazole 14 as white pow-
der (0.49 g, 82%) mp 39–40 8C. IR (neat): 3648, 3093, 2956, 2926,
2852, 2360, 1716, 1684, 1558, 1466, 1371, 1329, 1204, 1146, 1058,
1027, 991, 957, 886, 807, 703, 660 cmꢀ1. 1H NMR (300 MHz, CDCl3)
CDCl3) d: 0.87 (t, J 6.4 Hz, 3H, CH3), 1.25 (m, 8H, (CH2)4CH3), 1.32
(m, 4H, N1CH2CH2(CH2)2), 1.90 (tt, J 7.2, 6.8 Hz, 2H, N1CH2CH2),
2.42 (tt, 3JH–F 18.8, 3JH–H 6.8 Hz, 2H, OCH2CH2CF2), 3.82 (t, J 6.8 Hz,
2H, OCH2CH2CF2), 4.34 (t, J 7.2 Hz, 2H, N1CH2CH2), 4.67 (s, 2H, 4-
CH2O), 7.51 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d
: 13.9 (CH3),
d: 0.87 (t, J 6.8 Hz, 3H, CH3), 1.26 (m, 6H, (CH2)3CH3), 1.32 (m, 4H,
22.5 (CH2CH3), 26.4 (CH2), 28.9 (CH2), 29.0 (CH2), 29.2 (CH2), 30.2
(CH2), 31.4 (t, JC–F 20.9 Hz, OCH2CH2CF2), 31.7 (N1CH2CH2), 50.4
(N1CH2CH2), 62.1 (t, J 4.3 Hz, OCH2CH2CF2), 64.5 (4-CH2O), 122.2
(C5-H), 144.4 (C4). MS (ESI) m/z: 594.40 ([M+Na]+). Anal. Calcd. for
N1CH2CH2(CH2)2), 1.91 (tt, J 7.2, 6.8 Hz, 2H, N1CH2CH2), 4.03 (t,
3JH–F 13.6 Hz, 2H, OCH2CF2), 4.36 (t, J 7.2 Hz, 2H, N1CH2CH2), 4.81
2
(s, 2H, 4-CH2O), 7.55 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d: 13.9
(CH3), 22.5 (CH2CH3), 26.3 (CH2), 28.8 (CH2), 29.0 (CH2), 30.1 (CH2),
2
C20H26F13N3O requires: C, 42.04; H, 4.59; N, 7.35%. Found: C, 42.28;
31.7 (N1CH2CH2), 50.4 (N1CH2CH2), 65.6 (4-CH2O), 66.7 (t, JC–F
H, 4.65; N, 7.34%.
25.3 Hz, OCH2CF2), 122.6 (C5-H), 143.5 (C4). HR-MS (ESI): Calcd.
for 2 ꢁ C19H22F15N3O–2H+Na: m/z 1207.2790. Found: m/z
1207.2738 (2 ꢁ M–2H+Na]+, 9%); Calcd. for C19H22F15N3O+Na:
m/z 616.1422. Found: m/z 616.1422 ([M+Na]+, 100).
3.6.1.5. 1-n-Benzyl-4-(2-perfluorohexylethoxy)methyl-1H-1,2,3-
triazole 11. Benzyl azide (0.27 g, 2.03 mmol) to give 1-benzyl-4-(2-
perfluorohexylethoxy)methyl)-1H-1,2,3-triazole 11 as white flakes
(0.47 g, 88%) mp 53–55 8C. IR (KBr): 3566, 3128, 3090, 2909, 2362,
1717, 1559, 1458, 1367, 1235, 1209, 1189, 1142, 1091, 1060, 1012,
3.6.2.4. 1-n-Nonyl-4-(perfluoroheptylmethoxy)methyl-1H-1,2,3-
triazole 15. n-Nonyl azide (0.58 g, 3.43 mmol) to give 1-n-nonyl-4-
(perfluoroheptylmethoxy)methyl-1H-1,2,3-triazole 15 as a white
913, 860, 722, 699, 653 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d: 2.40 (tt,

904
D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
powder (0.49 g, 81%) mp 55–56 8C. IR (neat): 3134, 2954, 2921,
2849, 1560, 1467, 1371, 1329, 1206, 1147, 1132, 1105, 1026, 990,
886, 808, 703, 661 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d: 0.87 (t, J
Anal. Calcd. for C11H21N3O requires: C, 62.51; H, 10.04; N, 19.89%.
Found: C, 62.89; H, 10.30; N, 19.98%.
6.8 Hz, 3H, CH3), 1.26 (m, 8H, (CH2)4CH3), 1.32 (m, 4H,
N1CH2CH2(CH2)2), 1.91 (tt, J 7.2, 6.8 Hz, 2H, N1CH2CH2), 4.03 (t,
3JH–F 13.6 Hz, 2H, OCH2CF2), 4.36 (t, J 7.2 Hz, 2H, N1CH2CH2), 4.80
3.7.2. 1-n-Octyl-4-((prop-2-ynyloxy)methyl)-1H-1,2,3-triazole 31
Following a method reported by Jones et al. [36(a)], triazolyl
alcohol 30 (0.35 g, 1.7 mmol) was dissolved in dry DMF (10 mL)
and crushed NaOH pellets (0.25 g, 6.3 mmol) were added. The
mixture was stirred vigorously for 15 min in an ice bath under Ar,
then propargyl bromide (0.20 mL of 80% solution in toluene,
0.214 g, 1.8 mmol) was added dropwise and the heterogeneous
reaction mixture was stirred vigorously for 48 h, slowly warming
to r.t. H2O (30 mL) was added and the product was extracted with
EtOAc (4 ꢁ 50 mL). The organic phases were combined and washed
sequentially with 3% HCl (2 ꢁ 30 mL) and H2O (30 mL). The organic
phase was dried over Na2SO4 and evaporated to dryness under
reduced pressure. The resulting dark orange liquid (0.31 g) was
flash chromatographed over silica gel (Et2O/hexane, 50:50) to
generate (1-n-octyl-4-((prop-2-ynyloxy)methyl)-1H-1,2,3-triazole
31 as a pale orange oil (0.27 g, 67%), which decomposed upon
(s, 2H, 4-CH2O), 7.55 (s, 1H, H5). 13C NMR (75 MHz, CDCl3)
d: 13.9
(CH3), 22.5 (CH2CH3), 26.3 (CH2), 28.8 (CH2), 29.0 (CH2), 29.2 (CH2),
30.1 (CH2), 31.7 (N1CH2CH2), 50.4 (N1CH2CH2), 65.6 (4-CH2O), 66.7
(t, 2JC–F 25.3 Hz, OCH2CF2), 122.6 (C5-H), 143.5 (C4). MS (ESI) m/z:
1237.3211 ([2M+Na]+, 100%; 2 ꢁ C20H24F15N3O+Na requires m/z:
1237.3260), 630.1592 ([M+Na]+, 57; C20H24F15N3O+Na requires m/
z 630.1579). Anal. Calcd. for C20H24F15N3O requires: C, 39.55; H,
3.98; N, 6.92%. Found: C, 39.56; H, 3.94; N, 6.75%.
3.6.2.5. 1-n-Benzyl-4-(perfluoroheptylmethoxy)methyl-1H-1,2,3-
triazole 16. Benzyl azide (0.27 g, 2.03 mmol) to give 1-benzyl-4-
(perfluoroheptylmethoxy)methyl-1H-1,2,3-triazole 16 as white nee-
dles (0.42 g, 74%) mp 70–71 8C. IR (KBr): 3648, 3126, 3089, 1716,
1684, 1647, 1558, 1473, 1458, 1370, 1326, 1250, 1202, 1142, 1129,
1111, 1065, 1018, 990, 867, 723, 698, 659 cmꢀ1. 1H NMR (300 MHz,
attempted vacuum distillation. IR (neat)
2856, 2114, 1466, 1338, 1359, 1263, 1222, 1142, 1084, 1051, 1024,
942, 908, 891, 820, 784, 723, 665, 570 cmꢀ1 1H NMR (300 MHz,
CDCl3) : 0.84 (t, J 6.4 Hz, 3H, CH3), 1.27 (m, 10H, (CH2)5CH3), 1.87
vmax: 3290, 3138, 2926,
CDCl3)
d
: 4.02 (t, 3JH–F 13.9 Hz, 2H, OCH2CF2), 4.78 (s, 2H, 4-CH2O),
.
5.54 (s, 2H, N1CH2C6H5), 7.28 (m, 5H, N1CH2C6H5-ortho), 7.37 (m,
5H, N1CH2C6H5-para), 7.44 (m, 5H, N1CH2C6H5-meta), 7.50 (s, 1H,
d
(m, 2H, N1CH2CH2), 2.45 (t, J 2.4 Hz, 1H, OCH2CCH), 4.20 (d, J
2.4 Hz, 2H, OCH2CCH), 4.32 (t, J 7.2 Hz, 2H, N1CH2CH2), 4.71 (s, 2H,
4-CH2O), 7.54 (s, 1H, H5). 13C NMR (75 MHz)
d: 14.0 (CH3), 22.5
(CH2CH3), 26.4 (CH3), 28.9 (CH2), 29.0 (CH2), 30.2 (CH2), 31.6
(N1CH2CH2), 50.4 (N1CH2CH2), 57.4 (4-CH2O), 63.0 (OCH2CCH),
74.9 (OCH2CCH), 79.3 (OCH2CCH), 122.6 (C5-H), 144.2 (C4). MS
(ESI) m/z: 521.22 ([2M+Na]+, 15%), 273.03 ([M+H+Na]+, 17), 272.12
([M+Na]+, 100), 250.27 ([M+H]+, 15). Anal. Calcd. for C14H23N3O
requires: C, 67.43; H, 9.30; N, 16.86%. Found: C, 67.46; H, 9.61; N,
17.00%.
H5). 13C NMR (75 MHz, CDCl3)
d
: 54.2 (N1CH2C6H5), 65.6 (4-CH2O),
2
66.8 (t, JC–F 26.0 Hz, OCH2CF2), 122.7 (C5-H), 128.0 (N1CH2C6H5-
ortho), 128.8 (N1CH2C6H5-para), 129.1 (N1CH2C6H5-meta), 134.2
(N1CH2C6H5-ipso), 144.1 (C4). HR-MS (ESI) Calcd. for
2 ꢁ C18H12F15N3O+Na: m/z 1165.1380. Found: m/z 1165.1246
([2M+Na]+, 100%); Calcd. for C18H12F15N3O+Na: m/z 594.0639.
Found: m/z 594.0632 ([M+Na]+, 40); Anal. Calcd. for C18H12F15N3O
requires: C, 37.84; H, 2.12; N, 7.36%. Found: C, 37.91; H, 2.32; N,
7.19%.
3.7. Preparation of bis-triazolyl ethers 33–36
3.7.3. General method for the reaction of propargyl ether 31 with
perfluoroalkylethyl azides 17, 18 and 19 and perfluoroheptylmethyl
azide 32
3.7.1. 4-Hydroxymethyl-1-n-octyl-1H-1,2,3-triazole 30
Following a modification of the method of Rostovtsev et al.
[31(a)], CuSO4ꢂ5H2O (0.13 g, 2 mmol) and Na ascorbate (0.20 g,
1 mmol) were added to (CH3)2SO (20 mL) and the mixture stirred
for 5 min at r.t. Propargyl alcohol (1.24 mL, 1.20 g, 22 mmol) was
added dropwise with continued stirring, followed after 2 min by
dropwise addition of a solution of azide 24 (3.10 g, 20 mmol) in
(CH3)2SO (80 mL). The reaction mixture was heated in an oil bath at
65 8C for 24 h then quenched with H2O (50 mL) and extracted with
Et2O (3 ꢁ 50 mL). The organic phases were combined and washed
sequentially with brine (2 ꢁ 50 mL), H2O (50 mL), and more brine
(50 mL), then dried over Na2SO4, and evaporated to dryness under
reduced pressure. The resulting brown liquid crystallized at r.t. and
was flash chromatographed on silica gel using an Et2O/light
petroleum gradient (10:90 to 20:80). The major product (2.70 g)
was recrystallized from pentane to give 4-hydroxymethyl-1-n-
octyl-1H-1,2,3-triazole 30 as white plates (2.12 g, 50%) mp 40–42 8C
(lit. [35]: mp 46–49 8C). IR (Nujol) vmax 3310, 3208, 3132, 1336,
1297, 1257, 1220, 1212, 1147, 1055, 1043, 1017, 843, 784, 726,
Propargyl ether 31 (0.18 g, 0.72 mmol) and perfluorobutylethyl
azide 17 [13] (0.20 g, 0.69 mmol), perfluorohexylethyl azide 18
(0.28 g, 0.72 mmol), perfluorooctylethyl azide 19 [13] (0.34 g,
0.70 mmol) or perfluoroheptylmethyl azide 32 (0.31 g, 0.73 mmol)
were added to a stirred suspension of sodium ascorbate (0.022 g,
0.09 mmol) and CuSO4ꢂ5H2O (0.012 g, 0.045 mmol) in (CH3)2SO
(8 mL). The mixture was stirred with heating in a bath at 65 8C for
48 h. The reaction mixture was diluted with H2O (20 mL) and the
solution was extracted with CH2Cl2 (3 ꢁ 20 mL). The combined
organic layers were washed with H2O (2 ꢁ 10 mL), dried over
Na2SO4, and evaporated to dryness under reduced pressure. The
residue was rapidly column chromatographed on silica gel and the
major fraction recrystallized.
3.7.3.1. 4-(((1-n-Octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-
(perfluorobutyl)ethyl)-1H-1,2,3-triazole
33. Perfluorobutylethyl
azide 17 afforded the crude product as a low melting yellow
solid. The solid was chromatographed on silica gel and the major
fraction (0.21 g), eluted with 33:67 EtOAc/Et2O and recrystallized
from pentane, yielded 4-(((1-n-octyl-1H-1,2,3-triazol-4-yl)methox-
675, 657 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d: 0.86 (t, J 6.5 Hz, 3H,
CH2CH3), 1.24 (m, 6H, (CH2)3CH3), 1.30 (m, 4H, N1CH2CH2(CH2)2),
1.88 (tt, J 7.2, 6.9 Hz, 2H, N1CH2CH2CH2), 4.02 (s, 1H, OH), 4.33 (t, J
7.2 Hz, 2H, N1CH2CH2CH2), 4.77 (s, 2H, 4-CH2OH), 7.57 (s, 1H, H5).
y)methyl)-1-(2-(perfluorobutyl)ethyl)-1H-1,2,3-triazole 33 as
white crystalline powder (0.26 g, 70%) mp 68–70 8C. IR (Nujol):
max 2724, 2359, 1306, 1228, 1214, 1171, 1131, 1097, 1051, 1018,
989, 859, 815, 746, 724, 708 cmꢀ1 1H NMR (400 MHz, CDCl3)
a
13C NMR (75 MHz, CDCl3)
d
: 14.2 (CH3), 22.7 (CH2CH3), 26.6 (CH2),
v
29.05 (CH2), 29.14 (CH2), 30.3 (CH2), 31.8 (N1CH2CH2), 50.8
(N1CH2CH2), 56.2 (4-CH2OH), 122.0 (C5-H), 147.6 (C4). 13C NMR
(75 MHz, (CD3)2SO) d: 14.0 (CH3), 22.2 (CH2CH3), 25.9 (CH2), 28.5
(CH2), 28.6 (CH2), 29.9 (CH2), 31.3 (N1CH2CH2), 49.3 (N1CH2CH2),
55.2 (4-CH2OH), 122.7 (C5-H), 148.0 (C4). MS (ESI) m/z: 235.15
([M+H+Na]+, 12%); 234.20 ([M+Na]+, 100); 212.16 ([M+H]+, 7).
.
d:
0.85 (t, J 6.6 Hz, 3H, CH3CH2), 1.24 (m, 6H, (CH2)3CH3), 1.29 (m, 4H,
N10CH2CH2(CH2)2), 1.88 (tt, J 7.2, 6.9 Hz, 2H, N10CH2CH2CH2), 2.88
(tt, 3JH–F 18.0, 3JH–H 7.4 Hz, 2H, N1CH2CH2CF2), 4.32 (t, J 7.2 Hz, 2H,
N10CH2CH2CH2), 4.66 (dd, J 7.5, 7.4 Hz, 2H, N1CH2CH2CF2), 4.69 (s,
2H, 40-CH2O), 4.70 (s, 2H, 4-CH2O), 7.57 (s, 1H, H50 from N-alkyl

D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
905
ring), 7.68 (s, 1H, H5 from N-perfluorobutylethyl ring). 13C NMR
(100.1 MHz, CDCl3) 14.1 (CH3), 22.7 (CH2CH3), 26.6
which when eluted from the silica gel column with 33:67 EtOAc/
Et2O yielded 4-(((1-n-octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-
1-(2-(perfluoroheptyl)methyl)-1H-1,2,3-triazole 36 as white crystal-
line powder (0.15 g, 31%) mp 114–117 8C. 1H NMR (400 MHz,
d
:
(CH2CH2CH3), 29.0 (CH2), 29.1 (CH2), 30.3 (CH2), 31.78
2
(N10CH2CH2CH2), 31.82 (t, JC–F 21.8 Hz, N1CH2CH2CF2), 42.4 (t,
3JC–F 5 Hz, N1CH2CH2CF2), 50.7 (N10CH2CH2CH2), 63.48 (40-CH2O),a
63.53 (4-CH2O),a 123.0 (br, C50-H), 123.6 (C5-H) 144.3 (br, C40),
145.1 (C4). MS (ESI) m/z: 561.11 ([M+Na]+, 9%), 540.07 ([M+2H]+,
26), 539.15 ([M+H]+, 100), 538.53 ([M]+, 94). [aNote: assignments
CDCl3)
d
: 0.86 (t, J 6.5 Hz, 3H, CH3CH2), 1.25 (m, 6H, (CH2)3CH3),
1.30 (m, 4H, N10CH2CH2(CH2)2), 1.89 (tt,
J
6.7, 6.7 Hz, 2H,
N10CH2CH2CH2), 4.33 (t, J 7.2 Hz, 2H, N10CH2CH2CH2), 4.71 (s,
2H, 40-CH2O), 4.73 (s, 2H, 4-CH2O), 5.05 (t, 3JH–F 14.8 Hz, NCH2CF2),
7.58 (br s, 1H, H50 from N-alkyl ring), 7.78 (s, 1H, H5 from N-
of 13C NMR signals at
d 63.48 and 63.53 are likely, but might be
interchanged and could not be confirmed spectroscopically.] Anal.
Calcd. for C20H27F9N6O requires C, 44.61; H, 5.05; N, 15.61%. Found:
C, 44.79; H, 4.99; N, 15.64%.
perfluoroheptylmethyl ring). 13C NMR (100.1 MHz, CDCl3)
d: 14.1
(CH3), 22.7 (CH2CH3), 26.6 (CH2CH2CH3), 29.0 (CH2), 29.1 (CH2),
2
30.3 (CH2), 31.8 (N10CH2CH2CH2), 49.4 (t, JC–F 23 Hz, NCH2CF2),
50.8 (N10CH2CH2CH2), 63.5 (2C, 4-CH2O and 40-CH2O), 123.1 (br,
C50-H), 124.7 (C5-H) 144.4 (br, C40), 145.8 (C4). HR-MS (ESI) (Found
m/z: 1371.3598 ([2M+Na]+, 100%), 697.1727 ([M+Na]+, 28).
3.7.3.2. 4-(((1-n-Octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-
(perfluorohexyl)ethyl)-1H-1,2,3-triazole
34. Perfluorohexylethyl
azide 18 afforded the crude product as a pale yellow solid, which
when eluted from the silica gel column with 33:67 EtOAc/Et2O
afforded the major fraction that crystallized from pentane to yield 4-
(((1-n-octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-(perfluoro-
hexyl)ethyl)-1H-1,2,3-triazole 34 as white crystalline powder (0.21 g,
46%) mp 88–90 8C. IR (Nujol): vmax 3132, 3086, 1398, 1324, 1236,
1140, 1123, 1098, 1081, 1054, 1031, 1003, 989, 918, 850, 815, 728,
C
22H27N6OF13 requires m/z: 1371.3598 ([2M+Na]+), 697.1748
([M+Na]+). Anal. Calcd. for C22H25F15N6O2 requires C, 39.18; H,
3.74; N, 12.46%. Found: C, 39.18; H, 3.58; N, 12.25%.
3.8. Preparation of 4-(((1-n-nonyl-1H-1,2,3-triazol-4-
yl)methoxy)methyl)-1-(2-(perfluorooctyl)ethyl)-1H-1,2,3-triazole 38
714, 703, 660, 635, 567 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
0.85 (t, J
3.8.1. 4-Hydroxymethyl-1-n-nonyl-1H-1,2,3-triazole 37
6.6 Hz, 3H, CH3CH2), 1.22 (m, 6H, (CH2)3CH3), 1.28 (m, 4H,
N10CH2CH2(CH2)2), 1.86 (tt, J 7.3, 6.9 Hz, 2H, N10CH2CH2CH2),
2.79 (tt, 3JH–F 18.0, 3JH–H 7.5 Hz, 2H, N1CH2CH2CF2), 4.31 (t, J 7.3 Hz,
2H, N10CH2CH2CH2), 4.65 (dd, J ca. 7.5, ca. 7.4 Hz, 2H, N1CH2CH2CF2),
4.67 (s, 2H, 40-CH2O), 4.68 (s, 2H, 4-CH2O), 7.58 (s, 1H, H50 from N-
alkyl ring), 7.70 (s, 1H, H5 from N-perfluorohexyl ring). 13C NMR
Propargyl alcohol 29 (0.58 mL, 10 mmol) was added dropwise
to a solution of sodium ascorbate (0.178 g, 0.90 mmol) and
CuSO4ꢂ5H2O (0.112 g, 0.45 mmol) in (CH3)2SO (25 mL). The bright
yellow-green solution was stirred for 1 min before nonyl azide 25
(1.70 g, 10 mmol) was added dropwise, then stirring was contin-
ued in a bath at 70 8C for 36 h. The reaction mixture was diluted
with water (75 mL), extracted with EtOAc (3 ꢁ 50 mL), the
combined organic layers were washed with brine (2 ꢁ 25 mL),
dried over Na2SO4, and evaporated to dryness under reduced
pressure. The residue was flash chromatographed (silica gel, Et2O/
EtOAc 1:1) to give 4-hydroxymethyl-1-n-nonyl-1H-1,2,3-triazole 37
[38] (1.87 g, 79%) mp 55–57 8C (Et2O/light petroleum). IR (Nujol):
3301, 3195, 3131, 2922, 2853, 1463, 1376, 1218, 1144, 1055, 1046,
(100.1 MHz, CDCl3): d 14.0 (CH3), 22.6 (CH2CH3), 26.5 (CH2CH2CH3),
29.0 (CH2), 29.1 (CH2), 30.3 (CH2), 31.7 (N10CH2CH2CH2), 31.9 (t, 2JC–
3
21.7 Hz, N1CH2CH2CF2), 42.4 (t, JC–F 5.1 Hz, N1CH2CH2CF2), 50.6
F
(N10CH2CH2CH2), 63.46 (4-CH2O), 63.50 (40-CH2O), 122.9 (C50-H),
123.6 (C5-H), 144.3 (C40), 145.1 (C4). MS (ESI) m/z: 561.11 ([M+Na]+,
10%), 540.07 ([M+2H]+, 25), 539.11 ([M+H]+, 100), 538.86 ([M]+, 95).
Anal. Calcd. for C22H27F13N6O requires C, 41.38; H, 4.26; N, 13.16%.
Found: C, 41.58; H, 4.01; N, 13.04%.
1018, 724 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d: 0.84 (t, J 6.6 Hz, 3H,
CH2CH3), 1.22 (m, 8H, (CH2)4CH3), 1.27 (m, 4H, N1CH2CH2(CH2)2),
1.85 (tt, J 7.2, 6.9 Hz, 2H, N1CH2CH2CH2), 4.25 (s, 1H, OH), 4.29 (t, J
7.2 Hz, 2H, N1CH2CH2CH2), 4.74 (s, 2H, 4-CH2OH), 7.55 (s, 1H, H5).
3.7.3.3. 4-(((1-n-Octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-
(perfluorooctyl)ethyl)-1H-1,2,3-triazole
35. Perfluorooctylethyl
azide 19 afforded the crude product as a pale yellow solid, which
when eluted from the silica gel column with 33:67 EtOAc/Et2O
yielded 4-(((1-n-octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-
(perfluorooctyl)ethyl)-1H-1,2,3-triazole 35 as white crystalline
powder (0.21 g, 41%) mp 104–106 8C. IR (Nujol): vmax 3131,
3083, 2426, 2252, 1905, 1694, 1562, 1418, 1375, 1336, 1200, 1146,
1099, 1056, 1003, 989, 958, 907, 852, 824, 774, 736, 690, 654,
13C NMR (75 MHz, CDCl3)
d: 14.0 (CH3), 22.5 (CH2CH3), 26.4 (CH2),
28.9 (CH2), 29.1 (CH2), 29.2 (CH2), 30.1 (CH2), 31.7 (N1CH2CH2),
50.4 (N1CH2CH2), 55.9 (4-CH2OH), 121.7 (C5-H), 147.7 (C4). MS
(ESI) m/z: 473.11 ([2M+Na]+, 22%), 263.99 ([M+K]+, 7), 249.22
([M+H+Na]+, 16), 248.14 ([M+Na]+, 100), 226.18 ([M+H]+, 13). Anal.
Calcd. for C12H23N3O requires C, 63.99; H, 10.29; N, 18.65%. Found:
C, 63.59, H, 10.37; N, 18.29%.
560 cmꢀ1 1H NMR (400 MHz, CDCl3)
. d: 0.85 (t, J 6.8 Hz, 3H,
CH3CH2), 1.25 (m, 6H, (CH2)3CH3), 1.30 (m, 4H, N10CH2CH2(CH2)2),
1.88 (tt, J 7.2, 6.4 Hz, 2H, N10CH2CH2CH2), 2.81 (tt, 3JH–F 17.9, 3JH–H
7.5 Hz, 2H, N1CH2CH2CF2), 4.33 (t, J 7.2 Hz, 2H, N10CH2CH2CH2),
4.66 (dd, J 7.7, 7.4 Hz, 2H, N1CH2CH2CF2), 4.70 (s, 4H, 4-CH2O and
40-CH2O), 7.58 (s, 1H, H50 from N-alkyl ring), 7.69 (s, 1H, H5 from N-
3.8.2. 1-n-Nonyl-4-((prop-2-ynyloxy)methyl)-1H-1,2,3-triazole 38
Alcohol 37 (0.53 g, 2.35 mmol) was dissolved in DMF (10 mL)
and powdered NaOH pellets (0.32 g, 8.0 mmol) were added. The
contents were stirred in a salt-ice bath for 10 min then propargyl
bromide (0.25 mL, 2.82 mmol) was added dropwise. The reaction
mixture allowed to stir for 24 h, gradually warming to r.t. The
reaction mixture was partitioned between Et2O (30 mL) and water
(50 mL) and the aqueous layer extracted with more Et2O
(3 ꢁ 30 mL). The combined organic extracts were dried over
Na2SO4, and evaporated to dryness under reduced pressure. The
residue was flash chromatographed (silica gel, Et2O/light petro-
leum 1:1) to give 1-n-nonyl-4-((prop-2-ynyloxy)methyl)-1H-1,2,3-
triazole 38 as needles (0.42 g, 68%) mp 77–79 8C (Et2O/light
petroleum). IR (Nujol): 3278, 3089, 2922, 2853, 2108, 1460, 1376,
perfluorooctyl ring). 13C NMR (100.1 MHz, CDCl3)
d: 14.1 (CH3),
22.7 (CH2CH3), 26.6 (CH2CH2CH3), 29.0 (CH2), 29.1 (CH2), 30.4
(CH2), 31.8 (N10CH2CH2CH2), 31.9 (t, 2JC–F 22.0 Hz, N1CH2CH2CF2),
3
42.4 (t, JC–F 4.1 Hz, N1CH2CH2CF2), 50.7 (N10CH2CH2CH2), 63.51
(4-CH2O) 63.54 (40-CH2O), 123.0 (C50-H), 123.7 (C5-H) 144.4 (C40),
145.2 (C4). MS (ESI) m/z: 561.11 ([M+Na]+, 10%), 540.07 ([M+2H]+,
25), 539.11 ([M+H]+, 100), 538.86 (M+, 95). Anal. Calcd. for
C24H27F17N6O2 requires C, 39.03; H, 3.69; N, 11.38%. Found: C,
38.88; H, 3.60; N, 11.20%.
1224, 1153, 1103, 1059, 1027, 935, 730 cmꢀ1
.
1H NMR (300 MHz,
3.7.3.4. 4-(((1-n-Octyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-
CDCl3) : 0.86 (t, J 6.9 Hz, 3H, CH2CH3), 1.24 (m, 8H, (CH2)4), 1.30
d
((perfluoroheptyl)methyl)-1H-1,2,3-triazole
36. Perfluoroheptyl-
(m, 4H, (CH2)2), 1.89 (tt, J 7.2, 7.0 Hz, 2H, CH2CH2N), 2.46 (t, J 2.4 Hz,
1H, OCH2CCH), 4.22 (d, J 2.4 Hz, 2H, OCH2CCH), 4.34 (t, J 7.2 Hz, 2H,
methyl azide 32 afforded the crude product as pale yellow solid,

906
D.V. Francis et al. / Journal of Fluorine Chemistry 132 (2011) 898–906
CH2N), 4.74 (d, J 0.5 Hz, 2H, 4-CH2O), 7.56 (s, 1H, H5). 13C NMR
(75 MHz, CDCl3) : 14.0 (CH3), 22.6 (CH2CH3), 26.4 (CH3), 28.9
Appendix A. Supplementary data
d
(CH2), 29.1 (CH2), 29.3 (CH2), 30.2 (CH2), 31.7 (N1CH2CH2), 50.5
(N1CH2CH2), 57.5 (4-CH2O), 62.9 (OCH2CCH), 74.9 (OCH2CCH),
79.2 (OCH2CCH), 122.6 (C5-H), 144.1 (C4). MS (ESI) m/z: 286.08
([M+Na]+, 39%), 264.24 ([M+H]+, 46). Anal. Calcd. for C15H25N3O
requires C, 68.40; H, 9.57; N, 15.95%. Found: C, 68.70; H, 9.84; N,
15.86%.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jfluchem.2011.07.002.
References
[1] E. Kissa, Fluorinated Surfactants. Synthesis, Properties, Applications, Marcel
Dekker, New York, 1994.
[2] P.D.I. Fletcher, Specialist Surfactants: Fluorinated and Semi-Fluorinated
Surfactants, Blackie, London, 1997.
[3] T. Hiyama, Organofluorine Compounds: Chemistry and Applications, Springer-
Verlag, Berlin, 2000.
[4] M.P. Krafft, F. Giulieri, J.G. Riess, Angew. Chem., Int. Ed. Engl. 32 (1993) 741–743.
[5] J.G. Riess, J. Drug Target 2 (1994) 455–468.
[6] M.P. Krafft, J.G. Riess, Cell. Mol. Biol. Lett. 1 (1996) 459–468.
[7] M.P. Krafft, J.G. Riess, Biochimie 80 (1998) 485–489.
[8] K. Matsuoka, Y. Moroi, Curr. Opin. Coll. Interface Sci. 8 (2003) 227–235.
[9] Y. Kondo, N. Yoshino, Curr. Opin. Coll. Interface Sci. 10 (2005) 88–93.
[10] J.N. Slaughter, K.M. Schmidt, J.L. Byram, S. Mecozzi, Tetrahedron Lett. 48 (2007)
3879–3882.
3.8.3. 4-(((1-n-Nonyl-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1-(2-
(perfluorooctyl)ethyl)-1H-1,2,3-triazole 39
Propargyl ether 38 (0.263 g, 1.0 mmol) and perfluorooctylethyl
azide 19 (0.49 g, 2.0 mmol) were added to a stirred suspension of
sodium ascorbate (0.018 g, 0.09 mmol) and CuSO4ꢂ5H2O (0.012 g,
0.048 mmol) in (CH3)2SO (15 mL). The mixture was stirred with
heating in a bath at 85 8C for 48 h. The reaction mixture was diluted
with H2O (30 mL), extracted with EtOAc (3 ꢁ 30 mL), and the
combined organic layers were washed with brine (2 ꢁ 20 mL),
dried over Na2SO4, and evaporated to dryness under reduced
pressure. The residue was flash chromatographed (silica gel, Et2O/
EtOAc 1:1) to yield 4-(((1-n-nonyl-1H-1,2,3-triazol-4-yl)methoxy)-
methyl)-1-(2-(perfluorooctyl)ethyl)-1H-1,2,3–triazole 39 as white
prisms (0.55 g, 73%) mp 117–119 8C (pentane). IR (Nujol): 3131,
3081, 2924, 2724, 1563, 1459, 1376, 1336, 1220, 1200, 1146, 1116,
¨
[11] S. Cosgun, M. Ozer, F. Hamdoune, C. Gerardin, S. Thiebaut, B. Henry, J. Amos, L.
Rodehu¨ ser, C. Selve, J. Fluorine Chem. 107 (2001) 375–386.
[12] A.R. Katritzky, T.L. Davis, G.W. Rewcastle, G.O. Rubel, M.T. Pike, Langmuir 4 (1988)
732–735.
[13] J.B. Nivet, R. Bernelin, M. Le Blanc, J.G. Riess, Eur. J. Med. Chem. 27 (1992) 891–898.
[14] Y.M. Wu, J. Deng, X. Fang, Q.Y. Chen, J. Fluorine Chem. 125 (2004) 1415–1423, see
for close analogy.
[15] E. Mayot, C. Ge´rardin-Charbonnier, C. Selve, J. Fluorine Chem. 126 (2005)
715–720.
1099, 1055, 1041, 1031, 1003, 988, 956, 850, 723 cmꢀ1
.
1H NMR
[16] Z. Kaleta, O. Egyed, T. Soo´s, Org. Biomol. Chem. 3 (2005) 2228–2230.
[17] S.M. Vyas, J. Tura´nek, P. Kno¨tigova´, A. Kasna´, V. Kvardova´, V. Koganti, S.E. Rankin,
B.L. Kuntson, H.-J. Lehmler, New J. Chem. 30 (2006) 944–951.
[18] O.M. Martin, S. Mecozzi, Tetrahedron 63 (2007) 5539–5547.
[19] K. Matsuoka, T. Yoshimura, T. Shikimoto, J. Hamada, M. Yamawaki, C. Honda, K.
Endo, Langmuir 23 (2007) 10990–10994.
[20] W. Zhang, C. Cai, Chem. Commun. (2008) 5686–5694.
[21] W. Zhang, D.P. Curran, Tetrahedron 62 (2006) 11837–11865.
[22] (a) A. Gheorghe, E. Cuevas-Yan˜ez, J. Horn, W. Bannwarth, B. Narsaiah, O. Reiser,
Synlett (2006) 2767–2770;
(b) T. Chinnusamy, O. Reiser, ChemSusChem 3 (2010) 1040–1042.
[23] Y.-W. Zhu, W.-B. Yi, C. Cai, J. Fluorine Chem. 132 (2011) 71–74.
[24] R.W. Read, X.-B. Wang, Chiang Mai J. Sci. 36 (2009) 247–257.
[25] Y. Huang, R.W. Read, X. Wang, Aust. J. Chem. 63 (2010) 802–807.
[26] R.W. Read, X. Wang, A structure–function study of the surface tension changes of
m-xylene in the presence of fluorous 1H-1,2,3-triazoles and tetrazoles, J. Fluorine
Chem., doi:10.1016/j.jfluchem.2011.07.030.
[27] M. Napoli, C. Fraccaro, A. Scipioni, J. Fluorine Chem. 51 (1991) 103–115.
[28] C.S. Rondestvedt Jr., G.L. Thayer Jr., J. Org. Chem. 42 (1977) 2680–2683.
[29] F. Szonyi, A. Cambon, J. Fluorine Chem. 42 (1989) 59–68.
[30] D.J. Wardrop, J. Fritz, Org. Lett. 8 (2006) 3659–3662, supplementary information.
[31] (a) V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless, Angew. Chem., Int. Ed.
41 (2002) 2596–2599;
(300 MHz, CDCl3) : 0.86 (t, J 6.9 Hz, 3H, CH3CH2), 1.25 (m, 8H,
d
(CH2)4CH3), 1.31 (m, 4H, N10CH2CH2(CH2)2), 1.90 (tt, J 7.3, 6.9 Hz,
2H, N10CH2CH2CH2), 2.82 (m, 2H, N1CH2CH2CF2), 4.34 (t, J 7.3 Hz,
2H, N10CH2CH2CH2), 4.68 (dd, J 7.5, 7.4 Hz, 2H, N1CH2CH2CF2), 4.72
(br s, 4H, 4-CH2O and 40-CH2O), 7.61 (br s, 1H, H50 from N-alkyl
ring), 7.71 (br s, 1H, H5 from N-perfluorooctyl ring). 19F NMR
(282 MHz, CDCl3)
d
: ꢀ81.2 (t, 3F), ꢀ114.5 (t, 2F), ꢀ122.2 (m, 6F),
ꢀ123.1 (s, 2F), ꢀ123.8 (s, 2F), ꢀ126.4 (m, 2F). 13C NMR (75 MHz,
CDCl3) d: 14.0 (CH3), 22.6 (CH2CH3), 26.4 (CH2CH2CH3), 28.9 (CH2),
29.1 (CH2), 29.3 (CH2), 30.2 (CH2), 31.75 (N10CH2CH2CH2), 31.80 (t,
2JC–F 22.1 Hz, N1CH2CH2CF2), 42.3 (br, N1CH2CH2CF2), 50.6
(N10CH2CH2CH2), 63.3 (40-CH2O) 63.4 (4-CH2O), 122.9 (C50-H),
123.5 (C5-H) 144.2 (C40), 145.0 (C4). MS (ESI) m/z: 791.43 ([M+K]+,
22%), 776.06 ([M+H+Na]+, 23), 774.98 ([M+H]+, 100), 752.87 (M+,
16). Anal. Calcd. for C25H29F17N6O requires C, 39.90; H, 3.88; N,
11.17%. Found: C, 39.95; H, 3.67; N, 11.09%.
(b) C.W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 67 (2002) 3057–3064;
(c) R. Huisgen, in: A. Padwa (Ed.), 1,3-Dipolar Cycloaddition Chemistry, Wiley,
New York, 1984, pp. 1–176;
Acknowledgements
This work was financially supported by Australian Research
Council Discovery Project Grant DP0346614 and the University of
New South Wales. High resolution mass spectrometric analysis for
this work was carried out at the Bioanalytical Mass Spectrometry
Facility, UNSW, and was supported in part by infrastructure
funding from the New South Wales Government as part of its co-
investment in the National Collaborative Research Infrastructure
Strategy. A.I.M. was generously supported through an Australian
Research Council Endeavour Postdoctoral Research Fellowship
Award. Ms. Berta Litvak is thanked for her English language
translation of Ref. [38].
(d) V.O. Rodionov, V.V. Fokin, M.G. Finn, Angew. Chem., Int. Ed. 44 (2005)
2210–2215.
[32] A.K. Feldman, B. Colasson, V.V. Fokin, Org. Lett. 22 (2004) 3897–3899.
[33] A.V. Maksikova, E.S. Serebryakova, L.G. Tikhonova, L.I. Vereshchagin, Chem.
Heterocycl. Compd. (1980) 1284–1285.
¨
`
[34] S. Ozc¸ubukc¸u, E. Ozkal, C. Jimeno, M.A. Pericas, Org. Lett. 11 (2009) 4680–4683.
[35] C.O. Kappe, E. Van der Eycken, Chem. Soc. Rev. 39 (2010) 1280–1290.
[36] (a) G.B. Jones, J.M. Wright, G. Hynd, J.K. Wyatt, P.M. Warner, R.S. Huber, A. Li,
M.W. Kilgore, R.P. Sticca, R.S. Pollenz, J. Org. Chem. 67 (2002) 5727–5732;
(b) B. Jin, Q. Liu, G.A. Sulikowski, Tetrahedron 61 (2005) 401–408.
[37] M. Abe, K. Morikawa, K. Ogino, H. Sawada, T. Matsumoto, M. Nakayama, Langmuir
8 (1992) 763–764.
[38] A.V. Maksikova, G.P. Sukjanov, L.I. Vereshchagin, G.A. Gareev, Izv. Vyssh. Uchebn.
Zaved., Khim. Khim. T 27 (1984) 172–177 (English translation).