Fluorous 1,2,3-Triazol-4-ylmethyl Amines and Amine Derivatives for Novel Surfactant Applications

Article abstract of DOI:10.1071/CH14458

A series of fluorous surfactants with additional functionality were generated through the attachment of substituents at the amino nitrogen atom of the surfactant moiety. Examples of molecules containing one and two triazole ring systems were synthesized through N-alkylation and N-acylation strategies.

Full text of DOI:10.1071/CH14458

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH14458
Fluorous 1,2,3-Triazol-4-ylmethyl Amines and Amine
Derivatives for Novel Surfactant Applications
A
A
A B
,
Dominic V. Francis, Jason B. Harper, and Roger W. Read
A
School of Chemistry, The University of New South Wales, Sydney, NSW 2052,
Australia.
B
Corresponding author. Email: r.read@unsw.edu.au
A series of fluorous surfactants with additional functionality were generated through the attachment of substituents at the
amino nitrogen atom of the surfactant moiety. Examples of molecules containing one and two triazole ring systems were
synthesized through N-alkylation and N-acylation strategies.
Manuscript received: 19 July 2014.
Manuscript accepted: 30 August 2014.
Published online: 7 October 2014.
Introduction
plus additional functionality. In this paper, we describe the
synthesis of a new generation of fluorous 1,2,3-triazole analo-
gues, in which the linking ether oxygen is replaced with a
nitrogen atom in the form of either an amine or an amide. The
nitrogen atom is used as an anchor for the attachment of
additional functional substituents with either potential bioac-
tive, reporter, shape-filling, or shape-matching roles, and the
molecules are expected to take on the features of so-called
ABC miktoarm star motifs.[16]
Polyfluorinated molecules have received widespread attention
as a result of the unusual surface activity they exhibit, in addi-
tion to other interesting physical and biological properties.[1–4]
Compared with their non-fluorinated counterparts, fluorous
molecules are more efficient self-aggregators and are inherently
capable of self-aggregating to form stable, well-organised three-
dimensional supramolecular assemblies such as multilayered
structures, micelles, and tubules.[1,5–10] These characteristics
have made traditional fluorous surfactants highly suitable for
biomedical use as adjuvants in blood substitutes, as diagnostic
agents and carriers in drug delivery, and in industrial applica-
tions as firefighting foams and antifogging agents.[1–3,8,9,11–13]
The small size of fluorine atoms, their extreme electronega-
tivity, and the rigidity of perfluorinated segments of poly-
fluoroalkyl chains endow molecules that contain them with
exceptional aggregation properties in water and segregation
ability from hydrocarbon chains from the same or nearby
molecules. The physicochemical properties of perfluoroalkyl-
substituted compounds have been reviewed,[14–17] and pioneer-
ing work on the ability of fluorinated surfactants to form unusual
structures, including stable vesicles using single-chain surfac-
tants[18] and tubules with various morphologies and character-
istics[19,20] is noteworthy.
Recently, we have reported the potential of heterocycles
with attached fluorous chains as surfactants and participants in
self-assembly,[12] and have described the synthesis of 1,2,3-
triazoles[2,12,21] and tetrazoles[2] with one perfluoroalkyl sub-
stituent and either one n-alkyl, one n-alkoxymethyl, or one
methoxytriethylenoxymethyl substituent. Surface tension mea-
surements of the various substituent combinations revealed that
surfactants bearing fluorophilic and hydrophilic partner substi-
tuents exhibit the greatest surface activity.[22] However, we wish
to extend the capabilities of these surfactants through the
addition of functionality. One way to achieve this involves
changing the molecular design from the previously used ether-
linked systems[2,12,21] to those that are capable of accommo-
dating the necessary fluorophilic and hydrophilic substituents,
Results and Discussion
As a first approach to constructing nitrogen-bearing surfactant
systems, N-propargylphthalimide 1[23] was treated with each of
the azides 2–5[12] under standardized copper-catalyzed azide-
alkyne cycloaddition (CuAAC) conditions.[12] Phthalimide
derivatives 6–9 were obtained in acceptable yields, though these
yields decreased with increasing fluorous chain length after
workup (Scheme 1). Although yields declined, it was noted
that there was no apparent correlation between the length of the
perfluoroalkyl chain, or fluorine content (defined as percentage
fluorine by weight vs formula weight), and the melting points of
the homologous phthalimides 6–9. This suggested that the
packing density in the polyfluoroalkyl triazolyl phthalimide
series was not related to the CF2 chain length.
Treatment of phthalimides 6–9 with hydrazine hydrate in
ethanol at reflux for a standard 16 h gave the desired amines 10–
12, but not amine 13. Again, yields were inversely proportional
to CF2 chain length and fluorine content, but in this case, there
was also a correlation with melting point (Scheme 1). Despite
several attempts at different temperatures (08C to reflux) and
reaction times (16 to 72 h), the hydrazinolysis of phthalimide 9
did not give the corresponding amine 13 in practical quantities
(,10 % conversion to the desired amine 13 in each case),
presumably owing to poor solubility of the starting material.
Despite the disappointing result for amine 13, the new phthali-
mide 6–9 and amine 10–12 derivatives represented valuable
additions to a small library of readily available synthetic
Journal compilation Ó CSIRO 2014
www.publish.csiro.au/journals/ajc

B
D. V. Francis, J. B. Harper, and R. W. Read
N
RF
N
O
N
N
RF
N
N
i
ii
RF N3
N
NH2
O
F
Yield
[%]
76
mp
F
Yield
[%]
80
mp
RF
RF
[ЊC]
[%]
RF
[ЊC]
[%]
136–38 36.1
148–50 43.0
142–44 46.7
131–33 47.9
94–96 49.7
103–05 55.6
118–20 59.3
2
3
4
5
C4F9CH2CH2
C6F13CH2CH2
C7F15CH2
6
7
8
9
C4F9CH2CH2
C6F13CH2CH2
C7F15CH2
10 C4F9CH2CH2
11 C6F13CH2CH2
68
58
61
27
C7F15CH2
12
13
C8F17CH2CH2
46
C8F17CH2CH2
<10
C8F17CH2CH2
–
59.3
·
Reagents & conditions: i. N-propargylphthalimide 1, CuSO4 5H2O, sodium
·
ascorbate, DMSO, 80ЊC, 16 h; ii. NH2NH2 H2O, EtOH, reflux, 16 h.
Scheme 1.
N
N
RF
RF
N
N
N
N
i, ii or iii
NHCOR
NH2
Yield [%]
40
RF
RF
COR
14 C4F9
COCH2Cl
10
11
C4F9
C4F9
COCH2CH2Cl
C6F13
67
56
15
16
C6F13 COCF3
Reagents & conditions: i. CICOCH2Cl, PhNMe2, THF, reflux, 16 h; ii. CICOCH2CH2Cl,
PhNMe2, THF, reflux, 16 h; iii. (CF3CO)2O, no solvent, N2, rt, 16 h.
Scheme 2.
building blocks from which to elaborate the desired surfactant-
like molecules.
reaction at reflux gave again only traces of the acrylamide 20,
but a much decreased yield of the desired amide 19.
Thus, indications had been obtained that potentially useful
amide analogues of hybrid fluorous–hydrophilic monotriazolyl-
methyl-based surfactant molecules could be generated, and a
pathway to a useful acrylamide intermediate 20 had been
revealed.
N-Alkylation of trifluoroacetamide 16 using mesylate 21 was
investigated, but without success. Several methods using com-
binations of base and solvent at different temperatures gave only
recovery of the starting amide 16 or, in a few cases, loss of
material. This outcome was attributed to a lack of nucleophili-
city of the anion derived from amide 16. As a consequence, this
approach to nitrogen analogues was abandoned in favour of
direct amine N-alkylation (see below).
Utilization of Amide Derivatives
As a next step in this first approach to desired aza-analogues
of the previously prepared ether systems, three amide deriva-
tives 14–16 were synthesized by conventional methods
(Scheme 2).[24] Amides themselves can serve as a linker to
other groups or they can be reduced to alkylamines to retain
amine character in either secondary or tertiary form in the
linker. Secondary amides can also be useful as intermediates
for electrophilic attachment of groups to generate tertiary
amides.
Reaction of chloroalkanamides 14 and 15 with commercially
available methoxydiethylenoxyethanol 17 (Chart 1) in the
presence of base was investigated as a route to hydrophilic
monotriazoles 18 and 19 (Chart 1) respectively. Amide 14 with
alcohol 17 and excess potassium bis(trimethyldisilyl)amide
Direct N-Alkylation Strategy
As an alternative to preparation of amide derivatives and the use
of amide 16 as an intermediate for N-alkylation, direct N-
alkylation of the primary amine 10 was examined. Treatment of
amine 10 with an equimolar quantity of mesylate 21 in combi-
nations of potassium carbonate in either dry DMF at 408C or
acetonitrile at reflux for 16 h gave inseparable mixtures of the
secondary and tertiary amine products 22 and 23 (Chart 1),
1
(KHMDS) gave what appeared from H NMR spectroscopy
and mass spectrometry to be the anticipated derivative 18 in
43 % yield from reaction at room temperature, but only 28 %
yield from reaction at reflux. In contrast, near-identical treat-
ment of amide 15 at room temperature with equimolar or two-
fold equivalents of KHMDS each gave 48 % yield of acrylate 20
(Chart 1), rather than of the homologous amide 19. This result
suggested that the conditions were too basic and led to compet-
ing elimination. Use of a two-fold equivalent of the alcohol 17
and N,N-dimethylaminopyridine (DMAP) in place of KHMDS
at room temperature afforded only traces of the elimination
product 20 but 55 % yield of what was deduced from 1H NMR
spectroscopy to be the desired amide 19. Repetition of the
1
based on H NMR spectroscopic analyses. Normally, excess
amine reactant would be used in such circumstances when
monoalkylation was sought, but in this case, the fluorous amine
was precious and of limited supply. An attempt was therefore
made to use a fluorous solvent, perfluorohexane, to increase the
availability of fluorous amine 10 reactant in the presence of the
hydrophilic mesylate 21, and triethylamine was employed in

Fluorous Triazolylmethylamines for Surfactant Applications
C
Me
RO
N
N
C4F9
C4F9
O
N
N
N
N
3
H
N
H
N
Me
OR
O
3
17 OH
O
20
22
21 OSO2Me
N
C4F9
Me
N
C4F9
N
N
N
N
O
H
N
3
O
n
Me
N
O
3 Me
O
n
1
18
19
23
3
O
2
Chart 1.
Me
O
N
O
O
N
N
Me
Me
O
OHC
2
O
O
N
O
2
2
R
R
O
24
37
25 CHO
26 CH2OH
Chart 2.
place of the highly insoluble carbonate base; this arrangement
might have limited the supply of the alkylating agent. In prac-
tice, vigorous stirring for 16 h gave a similar mixture of the same
products, 22 and 23, with 82 % mass recovery. This approach
was also abandoned.
believed to be the corresponding acid 35, and pyridinium
dichromate gave no reaction at all.
It was concluded from these positive results that there were
significant issues with the oxidation of the previous hydrophilic
alcohols 17 and 26, or the stability of the aldehydes 24 and 25,
that had not been resolved, but these issues were not evident in
the fluorous triazolylmethyl alcohols and their corresponding
aldehydes.
Reductive Amination Strategy
Yet another approach to mono- and bis-triazolylmethyl amines
was envisaged through reductive amination. This would be
most efficient if achieved in one pot, but could also proceed in
two steps through isolation of intermediate imines from com-
bination of aldehyde and amine partners. With the availability
of the fluorous triazolylmethyl amines 10 and 12, and poten-
tially 13, attention turned to hydrophilic aldehyde partner 24
(Chart 2),[25–27] and eventually aldehyde 25 through alcohol 26
(Chart 2). In our hands, none of the literature Swern oxidation
methods[25–27] gave useful quantities of aldehyde 24 from
alcohol 17. Each of these methods gave mixtures of aldehyde 24
and alcohol 17, of which 5–30 % was aldehyde 24, and varying
reactant proportions did not improve the yield of aldehyde 24.
It was decided to swap the character of the reductive amina-
tion components. This required (i) the preparation of fluorous
triazolylmethyl alcohols and selective oxidation to their corre-
sponding aldehydes, and (ii) synthesis of complementary,
hydrophilic amine partners.
Meanwhile, known amine 36[28] was successfully synthe-
sized from methoxydiethylenoxyethanol 17 via its phthalimide
derivative 37 (Chart 2), which was prepared through a Mitsu-
nobu reaction,[29] and subsequent hydrazinolysis.[30] It was
isolated but used in subsequent reactions without purification.
Initial attempts to reductively aminate aldehyde 34 with
amine 36 in THF via imine 38 in the presence of excess sodium
triacetoxyborohydride under a variety of conditions of tempera-
ture, time, pre- and post-formed reagent, and sequential addition
of reactants failed to give any of the desired secondary amine 39.
Utilization of two mole equivalents of the more vigorous reagent
sodium borohydride in THF also failed. However, identical
treatment with sodium borohydride in ethanol rather than THF
gave complete conversion to the desired amine 39. Further
optimization showed the need for one full mole equivalent of
sodium borohydride for complete conversion, whereupon the
product 39 was isolated in 48 % yield (Scheme 3).
Commercial fluorous iodides 27–29 were transformed in situ
to the corresponding azides and subsequently via CuAAC with
propargyl alcohol into alcohols 30–32. In addition, preformed
fluorous azide 5 was transformed by a near-identical CuAAC
process into alcohol 33.
A variety of oxidizing agents and conditions were tested with
the representative alcohol 31. Optimum yields and minimum
technical difficulties were obtained using commercially avail-
able manganese dioxide. Under these conditions, aldehyde 34
was obtained as a white powder in 89 % yield at full conversion
(Scheme 3), whereas Jones reagent and Dess–Martin period-
inane conditions gave 58 and 53 % respectively of what was
With a successful strategy to the desired hybrid fluorous–
hydrophilic monotriazolylmethyl amines in place, efforts were
made to extend it to equivalent bis(triazolylmethyl)amines.
Thus, as an example, the known hydrophilic azide 40[31] was
treated with N-propargylphthalimide 1 under the previously
described CuAAC conditions in DMSO and the resultant
N-(4-triazolylmethyl)phthalimide 41 was converted using hydra-
zinolysis into hydrophilic triazolylmethylamine 42 as an orange
oil in 45 % overall yield. Unfortunately, amine 42 could not be
purified using chromatography; however, a portion was charac-
terized as its crystalline oxalate salt 43. The remaining amine 42
reacted with fluorous triazolylcarboxaldehyde 34 under CuAAC

D
D. V. Francis, J. B. Harper, and R. W. Read
N
N
RF
C6F13
N
N
N
N
i
ii
RF
l
OH
R
RF
RF
C4F9CH2CH2
Yield [%]
89
Yield [%]
89
R
C4F9CH2CH2
C6F13CH2CH2
C8F17CH2CH2
CHO
34
(35 CO2H)
27
28
29
30
31
C6F13CH2CH2
C8F17CH2CH2
C7F15CH2
95
33
47a
32
33
iii (a)
aSynthesised from preformed azide 5.
N
C6F13
N
C6F13
N
N
N
N
iii (b)
48 %
NH
N
Me
H2N
O
3
O
Me
O
Me
36
39
38
3
3
·
Reagents & conditions: i. propargyl alcohol, CuSO4 5H2O, sodium ascorbate,
DMSO, 65–85ЊC, 16 h; ii. MnO2, benzotrifluoride, reflux, 16 h; iii. (a) 34 and 36, EtOH,
reflux, 1 h, then cool to 0ЊC; (b) NaBH4, warm to rt, 16 h.
Scheme 3.
O
Me
Me
O
N
3
O
N
N
N
3
O
i
ii
73 %
N
N
N3
Me
3
N
62 %
H2N
40
41
42
O
iii
33 %
O
Me
Me
O
N
3
N
N
3
N
N
C6F13
N
N
N
N
ϩ
Ϫ
Ϫ
–
2 ϫ H3N
O2C CO2
H
N
43
44
·
Reagents & conditions: i. N-propargylphthalimide 1, CuSO4 5H2O, sodium ascorbate,
·
DMSO, 65ЊC, 16 h; ii. NH2NH2 H2O, EtOH, reflux, 16 h; iii. (a) 34, EtOH,
reflux, 1 h, then cool to 0ЊC; (b) NaBH4, warm to rt, 16 h.
Scheme 4.
conditions in DMSO to afford the bis(triazolylmethyl)amine 44
in 48 % yield as a pale white powder after chromatography and
recrystallization (Scheme 4).
N-Alkylation provided a relatively direct method of linear
derivatization. Monotriazolylmethylamine 39 was treated sepa-
rately with commercially sourced ethyl 4-bromobutyrate 45 and
readily prepared 6-galactosyl triflate 46 under identical condi-
tions, in acetonitrile at reflux in the presence of triethylamine.
The anticipated tertiary amines 47 and 48 were isolated in 65 and
61 % yields respectively (Scheme 5).
Linear acylation was also a means of attaching substituents to
amines. Other studies have shown that the secondary amine
function of molecules like amines 39 and 44 can participate in
preferential protonation.[32–34] Here, the generation of an amide
product would provide a less basic nitrogen linker group, and
one that might behave differently to changes in the pH of the
medium. In this situation, they might adopt a different geometry
to the amines already prepared, thereby introducing another
Functionalization of Hybrid Triazolylmethyl
Amines 39 and 44
A small variety of representative functional substituents clas-
sified as neutral (ethoxy carbonylpropanyl and 1-adamantanoyl)
and or bioactive (a-D-pyranogalactosyl) groups were selected
for attachment to amines 39 and 44. Although bioactive groups
have obvious applications, neutral groups were also an attractive
option because they could serve in either a space-filling or a
shape-matching role, or generate a face on a self-assembled
aggregate that might be either attractive or repellent to the
surroundings.

Fluorous Triazolylmethylamines for Surfactant Applications
E
(a)
i
ii
N
N
C6F13
C6F13
N
N
39
N
N
65 %
61 %
N
N
Me
Me
O
O
3
3
O
iii
47 %
CO2Et
C6F13
O
O
47
O
O
O
N
48
N
N
OSO2CF3
O
O
N
Me
O
3
O
O
46
50
44
O
(b)
O
Me
O
Me
N
N
N
N
C6F13
C6F13
ii
3
3
N
N
N
N
N
N
N
N
N
i
N
O
26 %
40 %
52
CO2Et
53
O
O
O
O
Reagents & conditions: i. BrCH2CH2CH2CO2Et 45, Et3N, CH3CN, reflux, 16 h; ii. 46,
Et3N, CH3CN, reflux, 16 h; iii. 1-adamantoyl chloride 49, Et3N, CH3CN, reflux, 16 h.
Scheme 5.
source of controlled variability in unimolecular species or
self-assembled aggregates. With these thoughts in mind, the
1-adamantoyl group, known for use in certain specialist antiviral
and anti-Parkinsonian drugs,[35] was introduced.
52, as a white powder, and galactopyranosyl amine derivative
53, as a highly viscous, colourless gum, in 26 and 40 % yields
respectively (Scheme 5).
1-Adamantane carbonyl chloride 49[36] was prepared in situ,
volatiles removed through distillation, and the reagent com-
bined with amine 39 in acetonitrile in the presence of 1.1 molar
equivalents of triethylamine. Reflux for 16 h, then aqueous
quenching and extractive workup gave a mixture of amide
derivative 50 and an unknown compound (51), which was
detected using thin-layer chromatography. After chromatogra-
phy, amide 50 was isolated in 47 % yield as a yellow oil, while a
slower-moving compound, deduced to be the original amine
hydrochloride salt 51, was recovered in 23 % yield. Although
identification of compound 51 was never confirmed, evidence
Conclusion
Satisfactory methods have been developed to new classes of
hybrid fluorous-polyether mono- and bis-(triazolylmethyl)
amine surfactant candidates. N-Alkylation of both and
N-adamantanoylation of the monotriazolylmethylamine have
provided a small library of novel surfactant-like molecules with
potential orthogonal functionality. Ultimately, one of the chal-
lenges will be to design such ABC miktoarm star molecules with
dominant self-assembly characteristics in the original A and B
arms of the star.[16,17] The surfactant properties and demon-
strated functionality of these novel compounds will be explored
in future work.
1
from the H NMR spectrum suggested that the compound did
not contain an adamantane moiety. The spectrum appeared very
similar to the 1H NMR spectrum for the starting material amine
39, except that the signal for the proton in the triazole ring had
shifted downfield dramatically from d 7.57 in amine 39 to d 8.55
in compound 51. Considering that the chemical shift for the
equivalent site in amide 50 was d 7.61, the significant downfield
shift of the triazole proton in compound 51 was likely to involve
charge on the triazole ring, possibly involving a shared proton
from the saturated linking amine group, rather than the presence
of a stronger electron-withdrawing group on the bridging nitro-
gen (see also ref. 14). Meanwhile, the high-resolution (HR)
electrospray ionization (ESI) mass spectrometric peak of com-
pound 51 m/z 591.1632 was almost identical to that of amine 39
m/z 591.1641 ([M þ H]þ) and elemental microanalysis was
consistent with the hydrochloride salt of amine 39.
Experimental
General
All reagents used in synthetic procedures were purchased from
either Sigma–Aldrich or Alfa Aesar and were used without fur-
ther purification. Quantities reported in the procedures involving
sodium hydride and/or propargyl bromide are based on 60 %
sodium hydride in mineral oil and 80 % propargyl bromide in
toluene respectively. KHMDS was used as a 0.5 M solution in
toluene. Hexane refers to n-hexane, whereas brine refers to a
saturated aqueous solution of sodium chloride. Organic solvents
were either used as received from Ajax Finechem or collected
from a PureSolv MD solvent purification system.
Thin-layer chromatographic analyses were conducted using
Merck TLC silica gel 60 F254 (0.2-mm) aluminium plates.
Visualization was performed using a UVP UVGL-58 ultraviolet
lamp at 254 nm where chromophores were available; otherwise,
Extrapolation of the N-alkylation process with bis(triazolyl-
methyl)amine 44 under identical conditions to those used for the
preparation of compounds 47 and 48 afforded the 4-aminobutyrate

F
D. V. Francis, J. B. Harper, and R. W. Read
either basic potassium permanganate stain[37] or ninhydrin in
ethanol[37] were used to develop TLC plates for analysis. Flash
column chromatography was performed on Merck silica gel 60
(0.040–0.063 mm), whereas flash column reverse-phase fluor-
ous chromatography was performed on FluoroFlashÒ silica gel
(0.040 mm).
Melting points were measured on a Mel-Temp II melting
point apparatus and are uncorrected. Microanalyses were car-
ried out by the Microanalytical Unit, Australian National
University. Infrared spectra were recorded using either a Nicolet
380 Fourier-transform (FT)IR instrument as either a Nujol mull
or as a neat film, or on a Cary 630 attenuated total reflectance
Fourier-transform infrared (ATR-FTIR) spectrometer as a neat
sample.
1H and 13C NMR spectroscopic characterization was per-
formed on either a Bruker DPX 300 MHz spectrometer (1H,
300 MHz; 13C, 75 MHz; 19F, 282 MHz) equipped with an auto-
sampler, a Bruker Avance III 400 MHz spectrometer (1H,
400 MHz; 13C, 100 MHz), or a Bruker Avance III 600 MHz
spectrometer (1H, 600 MHz; 13C, 150 MHz) equipped with an
autosampler. All chemical shifts are reported relative to tetra-
methylsilane. Mutiplicities are reported as either singlet (s),
doublet (d), doublet of doublets (dd), triplet (t), triplet of triplets
(tt), quartet (qr), quintet (q), or multiplet (m). Broad signals are
reported as br. Coupling constants (J, Hz) are reported for both
H–H and H–F coupling (where applicable); where not specified,
coupling constants refer to H–H coupling. Carbon atoms in the
perfluoroalkyl chains are not reported for any compounds, as the
low signal-to-noise ratio of these signals made it difficult to
accurately identify the relevant peaks.
42.4 (t, JC–F 5.1, C10), 123.59 (C5), 123.64 (C400 and C700), 132.1
(C300 and C800), 134.3 (C500 and C600), 143.3 (C4), 167.8 (C200 and
C900). dF (282 MHz, CDCl3) ꢁ81.5 (tt, JF–F 9.6, JF–F 2.5, 3F,
CF3CF2), ꢁ114.8 (m, 2F), ꢁ124.9 (m, 2F), ꢁ126.5 (m, 2F). m/z
(ESI) 496.78 ([M þ Na]þ, 100 %).
(ii) Azide 3 (1.38 g, 3.60 mmol) gave 1-(2-perfluorohexyl)
ethyl-4-phthalimidomethyl-1H-1,2,3,-triazole 7 as a white crys-
talline powder (1.55 g, 68 %), mp 148–1508C. Found: C 39.85,
H 2.02, N 9.65 %. C22H27N6OF13 requires: C 39.74, H 1.93, N
9.76 %. nmax (Nujol)/cmꢁ1 3085, 1460, 1402, 1348, 1250, 1185,
1138, 1100, 1071, 1037, 942, 772, 714, 702. dH (300 MHz,
CDCl3) 2.78 (tt, JH–F 17.6, J 7.5, 2H, H20), 4.63 (t, J 7.5, 2H,
H10), 4.98 (s, 2H, H100), 7.69 (s, 1H, H5), 7.71 (m, 2H, H500 and
H600), 7.83 (m, 2H, H400 and H700). dC (75 MHz, CDCl3) 31.9 (t,
JC–F 21.6, C20), 33.0 (C100), 42.4 (t, JC–F 5.1, C10), 123.6 (C5),
123.6 (C400 and C700), 132.1 (C300 and C800), 134.7 (C400 and C700),
143.3 (C4), 167.8 (C200 and C900). dF (282 MHz, CDCl3) ꢁ80.9
(tt, JF–F 10.0, JF–F 2.4, 3F, CF3CF2), ꢁ114.2 (m, 2F), ꢁ121.9 (m,
2F), ꢁ122.9 (m, 2F), ꢁ123.5 (m, 2F), ꢁ126.2 (m, 2F). m/z (ESI)
1171.70 ([2M þ Na]þ, 19), 598.28 ([M þ Na þ H]þ, 28), 597.37
([M þ Na]þ, 100 %).
(iii) Azide 4 (1.53 g, 3.60 mmol) gave 1-(2-perfluorooctyl)
ethyl-4-phthalimidomethyl-1H-1,2,3,-triazole 8 as a white
crystalline powder (1.34 g, 61 %), mp 142–1448C. Found:
C 37.38, H 1.71, N 9.23 %. C19H9N4O2F15 requires: C 37.39,
H 1.49, N 9.18 %. nmax (Nujol)/cmꢁ1 3130, 3082, 2853, 2337,
1963, 1872, 1819, 1774, 1702, 1612, 1547, 1433, 1404, 1340,
1292, 1257, 1240, 1221, 1178, 1125, 1140, 1100, 1082, 1055,
1046, 1027, 939, 840, 775, 758, 735, 713, 702, 655. dH
(400 MHz, CDCl3) 5.02 (t, JH–F 14.7, 2H, H10), 5.02 (s, 2H,
H100), 7.72 (m, 2H, H500 and H600), 7.80 (s, 1H, H5), 7.85 (m,
2H, H400 and H700). dC (100 MHz, CDCl3) 33.0 (C100), 49.4 (t,
JC–F 23.4, C10), 123.7 (C400 and C700), 124.8 (C5), 132.1 (C300
and C800), 134.3 (C500 and C600), 144.0 (C4), 167.7 (C200 and
C900). dF (282 MHz, CDCl3) ꢁ80.8 (tt, JF–F 9.9, JF–F 2.3, 3F,
CF3CF2), ꢁ116.8 (m, 2F), ꢁ121.6 (m, 4F), ꢁ122.7 (m, 4F),
ꢁ126.1 (m, 2F). m/z (ESI) 1243.08 ([2M þ Na]þ, 8), 633.11
([M þ Na]þ, 21 %).
Mass spectra were measured using the 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 methanol.
General Method for Preparation of
Phthalimides 6–9 and 40
Copper sulfate pentahydrate (0.05 mol equiv.), sodium ascor-
bate (0.12 mol equiv.), and DMSO (15 mL) were stirred together
at room temperature (rt) for 5 min. Phthalimide 1 (1.1 mol
equiv.) was added in one portion to the suspension with con-
tinuous stirring, followed after 1 min by a solution of the
appropriate azide (1.0 mol equiv.) in DMSO (5 mL). The reac-
tion mixture was heated at 808C for 16 h, then quenched with
H2O (50 mL) and the resulting mixture was extracted with
EtOAc (3 ꢀ 50 mL). The organic phases were combined and
washed with H2O (50 mL) and brine (2 ꢀ 50 mL), then dried
over Na2SO4 and evaporated to dryness under reduced pressure.
Column chromatography on silica gel (EtOAc/Et2O, 1 : 2), fol-
lowed by recrystallization from Et2O/hexane (2 : 1) gave the
desired products.
(i) Azide 2 (1.03 g, 3.6 mmol) gave 1-(2-perfluorobutyl)
ethyl-4-phthalimidomethyl-1H-1,2,3,-triazole 6 as a white, crys-
talline powder (1.48 g, 80 %), mp 136–1388C. Found: C 42.72,
H 2.21, N 11.56. C20H27N6OF9 requires: C 43.05, H 2.34, N
11.81 %. nmax (Nujol)/cmꢁ1 3469, 3124, 3080, 1774, 1716,
1616, 1561, 1402, 1356, 1325, 1291, 1219, 1184, 1162, 1133,
1106, 1091, 1072, 1055, 1034, 1014, 994, 942, 916, 901, 878,
848, 832, 775, 749, 716, 695, 671. dH (400 MHz, CDCl3) 2.78
(tt, JH–F 18.0, J 7.5, 2H, H20), 4.63 (t, J 7.5, 2H, H10), 4.99 (s, 2H,
H100), 7.70 (s, 1H, H5), 7.72 (m, 2H, H500 and H600), 7.83 (m, 2H,
H400 and H700). dC (100 MHz) 31.8 (t, JC–F 21.9, C20), 33.0 (C100),
(iv) Azide 5 (2.39 g, 3.60 mmol) gave 1-(2-perfluorooctyl)
ethyl-4-phthalimidomethyl-1H-1,2,3,-triazole 9 as a white
crystalline powder (0.86 g, 46 %), mp 131–1338C. Found: C
37.60, H 1.53, N 8.15 %. C21H11N4O2F17 requires: C 37.41, H
1.64, N 8.31 %. nmax (Nujol)/cmꢁ1 3468, 3131, 3086, 1772,
1615, 1558, 1401, 1346, 1251, 1213, 1144, 1111, 1100, 1074,
1054, 1037, 965, 942, 848, 772, 714, 656. dH (300 MHz, CDCl3)
2.79 (tt, JH–F 17.7, J 7.5, 2H, H20), 4.63 (t, J 7.5, 2H, H10), 5.00
(s, 2H, H100), 7.68 (s, 1H, H5), 7.72 (m, 2H, H500 and H600), 7.85
(m, 2H, H400 and H700). dC (75 MHz, CDCl3) 32.0 (t, JC–F 21.7,
C20), 33.1 (C100), 42.5 (t, JC–F 5.1, C10), 123.56 (C5), 123.61
(C400 and C700), 132.1 (C300 and C800), 134.3 (C500 and C600),
143.3 (C4), 167.8 (C200 and C900). dF (282 MHz, CDCl3) ꢁ80.7
(tt, JF–F 9.9, JF–F 2.1, 3F, CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.6 (m,
2F), ꢁ121.9 (m, 2F), ꢁ122.7 (m, 2F), ꢁ123.4 (m, 2F), ꢁ126.1
(m, 2F). m/z (ESI) 1371.10 ([2M þ Na]þ, 64), 697.00 ([M þ
Na]þ, 100 %).
(v) Azide 39 (3.07 g, 16.2 mmol) was reacted according to
the general procedure, but the product was chromatographed
using MeOH/EtOAc (2 : 98) to give 1-(2-(2-(2-methoxyethoxy)
ethoxy)ethyl)-4-phthalimidomethyl-1H-1,2,3-triazole 40 as an
orange oil (3.75 g, 62 %). Found: C 56.02, H 6.04, N 14.32.
C18H22N4O5ꢂ0.5H2O requires: C 56.38, H 6.05, N 14.62 %. m/z
(HR-MS ESI) 771.3066 ([2M þ Na]þ, 56), 397.1476 ([M þ
Na]þ, 100 %). C18H22N4O5 requires m/z 771.3078 ([2Mþ Na]þ),

Fluorous Triazolylmethylamines for Surfactant Applications
G
397.1488 ([Mþ Na]þ). nmax (ATR)/cmꢁ1 3136, 2870, 1769,
1707, 1611, 1550, 1465, 1426, 1392, 1325, 1293, 1221, 1189,
1096, 1047, 934, 846. dH (400MHz, CDCl3) 3.33 (s, 3H, H70),
3.49 (m, 2H, H60), 3.57 (m, 6H, H30–H50), 3.81 (t, J 5.2, 2H, H20),
4.47 (t, J 5.2, 2H, H10), 4.96 (s, 2H, H100), 7.68 (m, 2H, H500 and
H600), 7.76 (s, 1H, H5), 7.81 (m, 2H, H400 and H700). dC (100MHz,
CDCl3) 33.1 (C100), 50.3 (C10), 59.1 (C70), 69.4 (C20), 70.54 (C50),
70.57 (C40), 70.60 (C30), 71.9 (C60), 123.5 (C400 and C700), 124.0
(C5), 132.1 (C300 and C800), 134.1 (C500 and C600), 142.6 (C4),
167.7 (C200 and C900).
2F). m/z (ESI) 982.9 ([2M þ Na]þ, 10), 960.9 ([2M þ H]þ, 31),
502.9 ([M þ Na]þ, 16), 481.0 ([M þ H]þ, 100 %).
General Method for Preparation of Amides 14 and 15
Adapting the method of Cohen et al.,[24] the appropriate amine
(1.0 mol equiv.) and THF (100 mL) were stirred together at rt
before the sequential addition of N,N-dimethylaniline (0.6 mol
equiv.) and either chloroacetyl chloride or chloropropanoyl
chloride (2.5 mol equiv.). The reaction mixture was heated at
reflux for 16 h. The reaction was quenched with 5 % aq. K2CO3
(100 mL) and the resulting mixture extracted with EtOAc
(3 ꢀ 100 mL). The combined organic layers were washed with
sat. aq. NaHCO3 (2 ꢀ 100 mL) and brine (100 mL), then dried
over Na2SO4 and the solvent removed under reduced pressure.
The product was flash-chromatographed on reverse-phase
fluorous silica gel (MeOH) and recrystallized from EtOAc/
hexane (1 : 2).
(i) Amine 10 (3.86 g, 11.2 mmol) gave N-(((1-(2-perfluoro-
butyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-2-chloroacetamide
14 as a white powder (1.90 g, 40 %), mp 98–1008C. Found: C
31.73, H 2.40, N 13.23. C11H10N4OF9Cl requires: C 31.41, H
2.40, N 13.32 %. m/z (HR-MS ESI) 865.0639 ([2M þ Na]þ,
19 %), 863.0670 ([2M þ Na]þ, 33), 445.0243 ([M þ Na]þ, 33),
443.0279 ([M þ Na]þ, 100). C11H10N4OF9Cl requires m/z
865.0667 ([2M þ Na]þ), 863.0697 ([2M þ Na]þ), 445.0268
([M þ Na]þ), 443.0297 ([M þ Na]þ)). nmax (Nujol)/cmꢁ1 3335,
3142, 3077, 2724, 2336, 1934, 1864, 1650, 1541, 1399, 1336,
1294, 1227, 1170, 1133, 1098, 1081, 1054, 1018, 987, 925, 860,
833, 811, 777, 749, 707, 678. dH (300MHz, CD3OD) 2.92 (tt,
JH–F 19.1, J 6.9, 2H, H2000), 4.08 (s, 2H, H2), 4.49 (s, 2H, H10),
4.76 (t, J 6.9, 2H, H1000), 7.97 (s, 1H, H500). dC (75 MHz, CD3OD)
32.1 (t, JC–F 21.6, C2000), 35.9 (t, J 9.4, C10), 43.1 (t, J 1.8, C2),
43.4 (t, JC–F 5.2, C1000), 124.8, 125.4 (C500), 146.0, 146.1 (C400),
169.4 (C1). dF (282MHz, CD3OD) ꢁ82.7 (tt, JF–F 9.7, JF–F 3.4,
3F, CF3CF2), ꢁ115.6 (m, 2F), ꢁ125.6 (m, 2F), ꢁ127.2 (m, 2F).
(ii) Amine 10 (2.89 g, 8.40 mmol) gave N-(((1-(2-perfluoro-
butyl) ethyl)-1H-1,2,3-triazol-4-yl)methyl)-3-chloropropanamide
15 as a white powder (2.43 g, 67 %), mp 104–1068C. Found:
C 33.30, H 2.88, N 12.82. C12H12N4OF9Cl requires: C 33.16, H
2.78, N 12.89 %. m/z (HR-MS ESI) 457.0440 ([M þ Na]þ,
100 %. C12H12N4OF9Cl requires m/z 457.0454 ([M þ Na]þ).
nmax (ATR)/cmꢁ1 3286, 3149, 3082, 1634, 1553, 1453, 1443,
1397, 1357, 1333, 1290, 1255, 1225, 1211, 1169, 1129, 1096,
1048, 1017, 987, 960, 923, 857, 816. dH (400 MHz, CD3OD)
2.67 (t, J 6.4, 2H, H2), 2.90 (tt, JH–F 19.1, JH–H 7.1, 2H, H2000),
3.80 (t, J 6.4, 2H, H3), 4.46 (s, 2H, H10), 4.76 (t, J 7.1, 2H, H1000),
7.95 (s, 1H, H500). dC (100 MHz, CD3OD) 32.1 (t, JC–F 21.4,
C2000), 35.5 (C10), 39.8 (C2), 41.0 (C3), 43.4 (t, JC–F 4.8, C1000),
124.72, 124.73 (C500), 146.46, 146.47 (C400), 172.5 (C1).
General Method for Preparation of Amines 10–13
In a modification of the method of Butin et al.,[38] the appro-
priate phthalimide (1.0 mol equiv.) was dissolved in EtOH
(100 mL) with stirring. After 15 min, NH2NH2ꢂH2O (5.0 mol
equiv.) was introduced into the solution. The reaction mixture
was heated in an oil bath at reflux for 16 h, during which time a
white precipitate formed. The reaction mixture was cooled to rt
and the precipitate removed using vacuum filtration. The filtrate
was evaporated under reduced pressure and the resultant solid
flash-chromatographed on reverse-phase fluorous silica gel
(MeOH) and recrystallized from Et2O/hexane (1 : 2).
(i) Phthalimide 6 (3.00 g, 6.33 mmol) gave 4-aminomethyl-1-
(2-perfluorobutyl)ethyl-1H-1,2,3-triazole 10 as a white micro-
crystalline powder (1.66 g, 76 %), mp 94–968C. Found: C 31.49,
H 2.62, N 16.03. C9H9N4F9 requires C 31.41, H 2.64, N 16.28 %.
n
max (Nujol)/cmꢁ1 3331, 3145, 2854, 2360, 2338, 1950, 1872,
1704, 1596, 1545, 1403, 1358, 1297, 1231, 1216, 1172, 1132,
1098, 1050, 1019, 990, 859, 813, 756, 737, 721, 703. dH
(400 MHz, CD3OD) 2.93 (tt, JH–F 14.0, J 7.0, 2H, H200), 3.94
(s, 2H, H10), 4.78 (t, J 7.0, 2H, H100), 7.96 (s, 1H, H5). dC
(100 MHz, CD3OD) 32.1 (t, JC–F 21.4, C200), 37.3 (C10), 43.4 (t,
JC–F 4.9, C100), 124.0 (C5), 149.0 (C4). dF (282 MHz, CD3OD)
ꢁ82.7 (tt, JF–F 9.9, JF–F 3.2, 3F, CF3CF2), ꢁ115.7 (m, 2F),
ꢁ125.6 (m, 2F), ꢁ127.2 (m, 2F). m/z (ESI) 689.16 ([2M þ H]þ,
18), 367.17 ([M þ Na]þ, 13), 345.12 ([M þ H]þ, 100 %).
(ii) Phthalimide 7 (3.00 g, 5.22 mmol) gave 4-aminomethyl-
1-(2-perfluorohexyl)ethyl-1H-1,2,3-triazole 11 as a white
microcrystalline powder (1.34 g, 58 %), mp 103–1058C. Found:
C 29.90, H 2.07, N 12.34. C11H9N4F13 requires C 29.74, H 2.04,
N 12.61 %. nmax (Nujol)/cmꢁ1 3332, 3144, 2854, 2336, 1937,
1873, 1613, 1545, 1303, 1233, 1209, 1181, 1140, 1098, 1083,
1053, 1027, 991, 941, 908, 809, 701. dH (400 MHz, CD3OD)
2.94 (tt, JH–F 14.1, J 7.0, 2H, H200), 3.91 (s, 2H, H10), 4.78 (t, J
7.0, 2H, H100), 7.95 (s, 1H, H5). dC (100 MHz, CD3OD) 32.2 (t,
JC–F 21.4, C200), 37.4 (C10), 43.4 (t, JC–F 4.7, C100), 123.9 (C5),
149.6 (C4). dF (282 MHz, CD3OD) ꢁ82.4 (tt, JF–F 10.2, JF–F 2.1,
3F, CF3CF2), ꢁ115.4 (m, 2F), ꢁ122.9 (m, 2F), ꢁ123.9 (m, 2F),
ꢁ124.5 (m, 2F), ꢁ127.3 (m, 2F). m/z (ESI) 889.09 ([2M þ H]þ,
30), 446.13 ([M þ 2H]þ, 13), 445.07 ([M þ H]þ, 100 %).
(iii) Phthalimide 8 (3.00 g, 4.92 mmol) gave 4-aminomethyl-
1-(2-perfluoroheptyl)ethyl-1H-1,2,3-triazole 12 as a white
microcrystalline powder (0.62 g, 27 %), mp 118–1208C. Found:
C 27.24, H 1.63, N 11.65. C11H7N4F15 requires C 27.25, H 1.47,
N 11.65 %). nmax (Nujol)/cmꢁ1 3332, 3144, 2854, 2336, 1937,
1873, 1613, 1545, 1303, 1233, 1209, 1181, 1140, 1098, 1083,
1053, 1027, 991, 941, 908, 809, 701. dH (400 MHz, CD3OD)
3.95 (s, 2H, H10), 5.42 (t, JH–F 15.4, 2H, H100), 8.04 (s, 1H, H5).
dC (100 MHz, CD3OD) 37.4 (C10), 49.9 (t, JC–F 23.3, C100),
125.5 (C5), 150.0 (C4). dF (282 MHz, CD3OD) ꢁ82.9 (tt, JF–F
10.0, JF–F 2.4, 3F, CF3CF2), ꢁ117.8 (m, 2F), ꢁ122.7 (m, 2F),
ꢁ123.0 (m, 2F), ꢁ123.7 (m, 2F), ꢁ124.0 (m, 2F), ꢁ127.3 (m,
N-((1-(2-Perfluorohexyl)ethyl-1H-1,2,3-triazol-4-yl)methyl)
trifluoroacetamide 16
Amine 11 (2.95 g, 6.64 mmol) and (CF3CO)2O (9.22 mL,
66.4 mmol) were stirred together at 08C under nitrogen for
15 min before the mixture was allowed to warm to rt. After 16 h,
the excess reagent and volatiles were removed under reduced
pressure. The residue was flash-chromatographed on reverse-
phase fluorous silica gel (MeOH) and recrystallized from
EtOAc/hexane (1 : 19) to give N-((1-(2-perfluorohexyl)ethyl-
1H-1,2,3-triazol-4-yl)methyl)trifluoroacetamide 16 as a pale-
green powder (1.70 g, 56 %), mp 110–1128C. Found: C 28.94,
H 1.44, N 10.47. C13H8N4OF16 requires: C 28.90, H 1.49,

H
D. V. Francis, J. B. Harper, and R. W. Read
N 10.37 %. m/z (HR-MS ESI) 563.0317 ([M þ Na]þ, 100 %).
C13H8N4OF16 requires m/z 563.0340 ([M þ Na]þ). nmax (ATR)/
cmꢁ1 3313, 1692, 1544, 1430, 1395, 1348, 1332, 1290, 1230,
1178, 1136, 1079, 1054, 1035, 981, 917, 828, 789, 775, 730, 696,
656. dH (400 MHz, CDCl3) 2.93 (tt, JH–F 18.8, J 7.1, 2H, H2000),
4.54 (s, 2H, H10), 4.77 (t, J 7.1, 2H, H1000), 8.02 (s, 1H, H500). dC
(100 MHz, CDCl3) 32.2 (t, JC–F 21.2, C2000), 35.7 (t, JC–F 10.1,
C10), 43.5 (t, JC–F 5.3, C1000), 115.6 (q, JC–F 290, C2), 125.8
(C500), 144.97, 145.03 (C400), 158.8, 159.3 (C1). dF (282 MHz,
CDCl3) ꢁ77.4 (s, 3F, CF3CO), ꢁ82.5 (tt, JF–F 10.1, JF–F 2.5, 3F,
CF3CF2), ꢁ115.4 (m, 2F), ꢁ122.9 (m, 2F), ꢁ123.9 (m, 2F),
ꢁ124.6 (m, 2F), ꢁ127.4 (m, 2F).
N-Alkylation of Amine 10 with Mesylate 21
General Procedure: K2CO3 (0.48 g, 2.70 mmol) and amine 10
(1.20 g, 2.70 mmol) were stirred together in MeCN (20 mL) at rt
for 30 min. Mesylate 21 (0.58 g, 2.70 mmol) in MeCN (5 mL)
was added dropwise over 1 min. The reaction mixture was
stirred at rt for 2 h, then heated at reflux for an additional 16 h
before quenching with brine (25 mL). The product was extracted
into EtOAc (3 ꢀ 20 mL), and the combined organic layers were
dried over MgSO4. The solvent was removed under reduced
pressure to give a pale-yellow powder (0.98 g). Analysis using
1H NMR spectroscopy revealed a mixture of secondary amine
22 and tertiary amine 23, which could not be separated by
chromatography.
Treatment of Amides 14 and 15 with Alcohol 17
Under Basic Conditions
General Method for Preparation of Alcohols 30–32
2-(2-(2-Methoxyethoxy)ethoxy)ethanol 17 (0.49 mL, 3.04 mmol)
was dissolved in dry THF (10 mL) and the solution stirred under
nitrogen while cooled in ice for 15 min. KHMDS (8.30 mL of a
0.5 M solution in toluene, 4.15 mmol) was added dropwise by
syringe over 30 s, and the mixture was allowed to warm to rt.
After 1 h, a solution of amide 14 (1.16 g, 2.76 mmol) in dry THF
(10 mL) added by syringe over 1 min. The reaction was main-
tained at the specified temperature for 16 h, then quenched with
sat. aq. NH4Cl (30 mL) and the product extracted with EtOAc
(3 ꢀ 30 mL). The combined organic layers were washed with
saturated brine (2 ꢀ 30 mL), dried over MgSO4, and the solvent
removed under reduced pressure to yield crude amide 18 as a
yellow oil (0.61 g, 43 %). Purification was attempted using
flash-chromatography on reverse-phase fluorous silica gel
(MeOH), but the compound could not be purified.
Based on the method reported by Wang and Read,[12] the
appropriate iodide (1.0 mol equiv.) and DMSO (50 mL) were
stirred together for 2 min before dropwise addition of propargyl
alcohol over 30 s (2.5 mol equiv.). Copper sulfate pentahydrate
(0.1 mol equiv.) and sodium ascorbate (0.29 mol equiv.) were
added to the reaction mixture. After 2 min, NaN3 (3.0 mol
equiv.) was added and the stirred mixture was heated in an oil
bath at 658C for 16 h. The reaction mixture was quenched
with H2O (200 mL) and the resulting mixture was extracted with
EtOAc (3 ꢀ 100 mL). The organic fractions were combined,
washed with H2O (100 mL), brine (2 ꢀ 100 mL), dried over
Na2SO4, and the organic solvent was evaporated under reduced
pressure. The crude material was flash-chromatographed on
reverse-phase fluorous silica gel (MeOH) and recrystallized
from EtOAc/hexane (1 : 6).
Dry 2-(2-(2-methoxyethoxy)ethoxy)ethanol 17 (0.49 mL,
3.04mmol) and dry THF (10 mL) were stirred together under
nitrogen at 08C for 15 min. KHMDS (6.07 mL of a 0.5 M solution
in toluene, 3.35 mmol) was added dropwise by syringe over 30 s,
and the mixture was allowed to warm to rt. After 40 min, the
reaction mixture was transferred dropwise by syringe, over 30 s,
into a second flask containing a solution of amide 15 (1.2 g,
3.04mmol) in dry THF (10 mL) at 08C under nitrogen. The
reaction mixture was allowed to warm to rt and stirred for 16 h.
The reaction mixture was quenched with saturated aqueous
NH4Cl (20 mL) and the resulting mixture was extracted with
EtOAc (3 ꢀ 50 mL). The combined organic layers were washed
with brine (2 ꢀ 50 mL), dried over MgSO4, and the solvent was
evaporated under reduced pressure. The product was flash
chromatographed on reverse-phase fluorous silica gel (MeOH)
and the major product was recrystallized from EtOAc/hexane
(1 : 10)to give N-((1-(2-perfluorobutyl)ethyl-1H-1,2,3-triazol-4-
yl)methyl)acrylamide 20 as a yellow powder (0.47 g, 43 %), mp
107–1098C. Found: C 36.44, H 2.69, N 13.87. C12H11N4OF9
requires: C 33.19, H 2.78, N 14.07 %. m/z (HR-MS ESI)
819.1490 ([2M þ Na]þ, 37), 399.0869 ([M þ H]þ, 100%).
C12H11N4OF9 requires m/z 819.1476 ([2M þ Na]þ), 399.0867
([M þ H]þ). nmax (ATR)/cmꢁ1 3287, 3149, 3068, 1652, 1624,
1546, 1452, 1408, 1357, 1334, 1303, 1210, 1168, 1128, 1096,
1047, 1015, 986, 955, 856, 803. dH (400 MHz, CD3OD) 2.92 (tt,
JH–F 18.7, JH–H 7.0, 2H, H2000), 4.51 (s, 2H, H10), 4.76 (t, J 7.0,
2H, H1000), 5.67 (dd, J 6.9, 5.1, 1H, H20), 6.24 (s, 1H, H3b), 6.25
(d, J 1.8, 1H, H3a), 7.97 (s, 1H, H500). dC (100 MHz, CD3OD)
32.1 (t, JC–F 21.2, C2000), 35.6 (C10), 43.4 (t, JC–F 4.7, C1000), 124.8
(C500), 127.1 (C2), 131.7 (C3), 146.3 (C400), 168.1 (C1). dF
(282 MHz, CD3OD) ꢁ82.6 (tt, JF–F 9.5, 3.2, 3F, CF3CF2),
ꢁ115.6 (m, 2F), ꢁ125.5 (m, 2F), ꢁ127.2 (m, 2F).
(i) Iodide 27 (3.74 g, 10.0 mmol) gave 4-hydroxymethyl-1-
(2-perfluorobutyl)ethyl-1H-1,2,3-triazole 30 as a pale white
powder (3.02 g, 87 %), mp 48–508C. Found: C 31.26, H 2.28,
N 12.08. C9H8N3OF9 requires C 31.21, H 2.34, N 12.17 %. m/z
(HR-MS ESI) 713.0924 ([2M þ Na]þ, 24 %), 368.0407 ([M þ
Na]þ, 100). C9H8N3OF9 requires m/z 713.0945 ([2M þ Na]þ),
368.0421 ([M þ Na]þ. nmax (ATR)/cmꢁ1 3326, 3119, 3073,
1449, 1398, 1356, 1295, 1208, 1126, 1096, 1048, 1006, 853,
814. dH (400 MHz, CD3OD) 2.94 (tt, JH–F 18.7, J 7.0, 2H, H200),
4.68 (s, 2H, H10), 4.78 (t, J 7.0, 2H, H100), 8.00 (s, 1H, H5). dC
(100 MHz, CD3OD) 32.1 (t, JC–F 21.4, C200), 43.4 (t, JC–F 4.8,
C100), 56.5 (C10), 124.6 (C5), 149.4 (C4). dF (282 MHz, CD3OD)
ꢁ82.7 (tt, JF–F 10.1, JF–F 3.1, 3F, CF3CF2), ꢁ115.7 (m, 2F),
ꢁ125.6 (m, 2F), ꢁ127.2 (m, 2F).
(ii) Iodide 28 (4.74 g, 10.0 mmol) gave 4-hydroxymethyl-1-(2-
perfluorohexyl)ethyl-1H-1,2,3-triazole 31as a pale whitepowder
(4.23 g, 95%), mp 62–648C. Found: C 29.59, H 1.81, N 9.27.
C11H8N3OF13 requires C 29.68, H 1.81, N 9.44%. m/z (HR-MS
ESI) 913.0790 ([2M þ Na]þ, 58 %), 468.0338 ([M þ Na]þ, 100).
C11H8N3OF13 requires m/z 913.0817 ([2M þ Na]þ), 468.0357
([M þ Na]þ). nmax (ATR)/cmꢁ1 3327, 3120, 3073, 2869, 2321,
2190, 2108, 1852, 1551, 1450, 1398, 1365, 1316, 1291, 1196,
1177, 1135, 1079, 1049, 1007, 988, 916, 850, 776. dH (400MHz,
CD3OD) 2.94 (tt, JH–F 18.8, J 7.0, 2H, H200), 4.68 (s, 2H, H10),
4.78 (t, J 7.0, 2H, H100), 8.00 (s, 1H, H5). dC (100MHz, CD3OD)
32.2 (t, JC–F 21.4, C200), 43.4 (t, JC–F 4.8, C100), 56.5 (C10), 124.6
(C5), 149.4 (C4). dF (282MHz, CD3OD) ꢁ82.4 (tt, JF–F 10.2,
JF–F 2.0, 3F, CF3CF2), ꢁ115.4 (m, 2F), ꢁ122.9 (m, 2F), ꢁ123.9
(m, 2F), ꢁ124.5 (m, 2F), ꢁ127.3 (m, 2F).
(iii) Iodide 29 (5.74 g, 10.0mmol) gave 4-hydroxymethyl-1-
(2-perfluorooctyl)ethyl-1H-1,2,3-triazole 32 as a pale white
powder (1.00 g, 33%), mp 147–1498C. Found: C 28.56, H 1.41,

Fluorous Triazolylmethylamines for Surfactant Applications
I
N 8.03. C13H8N3OF17 requires C 28.64, H 1.48, N 7.71%. m/z
(HR-MS ESI) 568.0278 ([M þ Na]þ, 100 %). C13H8N3OF17
requires m/z 545.0396 ([M þ Na]þ). nmax (ATR)/cmꢁ1 3320,
3124, 3075, 2946, 2874, 2123, 1667, 1565, 1452, 1399, 1370,
1331, 1291, 1196, 1143, 1036, 987, 955, 842, 817, 766. dH
(400 MHz, CD3OD) 2.92 (tt, JH-F 18.7, J 7.3, 2H, H200), 4.68
(s, 2H, H10), 4.78 (t, J6.5, 2H, H100), 8.01 (s, 1H, H5). dC (100 MHz,
CD3OD) 32.2 (t, JC–F 21.4, C200), 43.4 (t, JC–F 4.9, C100), 56.5 (C10),
124.6 (C5), 149.4 (C4). dF (282 MHz, CD3OD) ꢁ82.4 (tt, JF–F
10.1, JF–F 1.8, 3F, CF3CF2), ꢁ115.4 (m, 2F), ꢁ122.8 (m, 2F),
ꢁ123.8 (m, 6F), ꢁ124.6 (m, 2F), ꢁ127.3 (m, 2F).
3F, CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.8 (m, 2F), ꢁ122.9 (m, 2F),
ꢁ123.4 (m, 2F), ꢁ126.2 (m, 2F).
General Method for Preparation of Amines 36 and 42
Following the method of Łowicki et al.,[30] the phthalimide
(1.0 mol equiv.) and NH2NH2ꢂH2O (2.0 mol equiv) were dis-
solved in EtOH (300 mL) and the solution was heated at reflux
for 4 h, at which point conc. HCl (3.5 mol equiv.) was added in
one portion. The reaction mixture was heated at reflux for a
further 16 h, then cooled to rt and filtered through Celite. The
filtrate was adjusted to pH 14 through the addition of KOH
pellets and extracted with CHCl3 (3 ꢀ 100 mL). The combined
organic layers were dried over MgSO4 and the solvent removed
under reduced pressure.
4-Hydroxymethyl-1-perfluoroheptylmethyl-1H-1,2,3-
triazole 33
(i) Phthalimide 37 (26.7 g, 91.0 mmol) gave 2-(2-(2-methoxy-
ethoxy)ethoxy)ethylamine 36 as a pale yellow oil (7.28 g, 49 %),
which was used without further purification. nmax (ATR)/cmꢁ1
2864, 1782, 1590, 1453, 1387, 1348, 1288, 1247, 1197, 1106,
1030, 982, 926, 844, 806. dH (300 MHz, CDCl3) 2.79 (t, J 3.6,
2H, H1), 3.30 (s, 3H, H50), 3.43 (m, 2H, H2), 3.49 (m, 2H, H40),
3.57 (m, 6H, H10–H30). dC (75 MHz, CDCl3) 41.7 (C1), 59.0
(C50), 70.2, 70.5, 70.6 (C10-C30), 71.9 (C40), 73.3 (C2).
Copper sulfate pentahydrate (0.20 g, 0.80 mmol) and sodium
ascorbate (0.44 g, 2.22 mmol) were stirred in DMSO (45 mL) for
2 min before propargyl alcohol (1.16 mL, 1.13 g, 20.2 mmol)
was added. After 1 min, a solution of azide 4 (4.90 g, 11.5 mmol)
in DMSO (5 mL) was added, and the reaction mixture was
heated in an oil bath at 808C for 16 h with stirring. The reaction
was quenched with H2O (200 mL) and the resultant mixture
extracted with EtOAc (3 ꢀ 100 mL). The organic fractions were
combined and washed with H2O (100 mL), brine (2 ꢀ 100 mL),
dried over Na2SO4, and the organic solvent was evaporated
under reduced pressure. Flash chromatography on reverse-phase
fluorous silica gel (MeOH) and recrystallization of the major
product from EtOAc/hexane (1 : 6) yielded 4-hydroxymethyl-1-
perfluoroheptylmethyl-1H-1,2,3-triazole 33 as pale white
powder (2.59 g, 47 %), mp 134–1368C. Found: C 27.09, H 1.42,
N 8.92. C11H6N3OF15 requires C 27.46, H 1.26, N 8.73 %. m/z
(HR-MS ESI) 481.0495 (Mþ, 100 %). C11H6N3OF15 requires
m/z 481.0271 ([M]þ). nmax (ATR)/cmꢁ1 3294, 3164, 3004,
2966, 2778, 2321, 2119, 2056, 2009, 1563, 1417, 1367, 1325,
1200, 1144, 1100, 1064, 1030, 934, 881, 822, 779, 730, 693. dH
(400 MHz, CD3OD) 4.72 (s, 2H, H10), 5.43 (t, JH–F 15.4, 2H,
H100), 8.07 (s, 1H, H5). dC (100 MHz, CD3OD) 49.9 (t, JC–F 23.4,
C100), 56.4 (C10), 126.1 (C5), 149.9 (C4). dF (282 MHz, CD3OD)
ꢁ82.4 (tt, JF–F 10.2, JF–F 2.5, 3F, CF3CF2), ꢁ117.9 (m, 2F),
ꢁ122.7 (m, 2F), ꢁ123.0 (m, 2F), ꢁ123.7 (m, 2F), ꢁ124.0 (m,
2F), ꢁ127.3 (m, 2F).
(ii) Phthalimide 41 (9.94 g, 26.5 mmol) gave 4-aminomethyl-
1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazole 42
as a slightly impure orange oil (4.73 g, 73 %), which was used
in later reactions without further purification. A portion of amine
42 (1.03 g, 4.22 mmol) was stirred together with oxalic acid
(0.267 g, 2.11 mmol) in EtOH (5 mL) for 2 h at rt. The solvent
was removed under vacuum and the remaining solid was
recrystallized from EtOH to give bis((1-(2-(2-(2-methoxy-
ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methylammonium)
oxalate 43 as a white powder (1.14 g, 48 %), mp 154–1568C.
Found: C 45.26, H 7.57, N 19.20. C22H42N8O10 requires: C
45.67, H 7.32, N 19.37 %. m/z (HR-MS ESI) 489.3140 ([2M þ
H]þ, 100), 245.1606 ([M þ H]þ, 100 %). C10H20N4O3 requires
m/z 489.3149 ([2M þ H]þ), 245.1614 ([M þ H]þ). nmax (ATR)/
cmꢁ1 3131, 3088, 2866, 2815, 2632, 1640, 1542, 1462, 1349,
1226, 1199, 1119, 1048, 980, 948, 856, 829, 770. dH (400 MHz,
D2O) 3.36 (s, 3H, H70), 3.59 (m, 2H, H60), 3.62 (m, 2H, H40 or
H50), 3.64 (m, 2H, H40 or H50), 3.67 (m, 2H, H30), 4.00 (t, J 5.2,
2H, H20), 4.35 (s, 2H, H100), 4.67 (t, J 5.2, 2H, H10), 8.17 (s, 1H,
H5). dC (100 MHz, D2O) 34.0 (C100), 50.1 (C10), 58.0 (C70), 68.6
(C20), 69.3 (C40 or C50), 69.4 (C40 or C50), 69.6 (C30), 70.9 (C60),
125.7 (C5), 139.7 (C4), 173.0 (C1000).
1-(2-Perfluorohexyl)ethyl-1H-1,2,3-triazole-4-
carbaldehyde 34
A mixture of alcohol 31 (8.39 g, 18.9 mmol) and a,a,a-
trifluorotoluene(50 mL) was stirredtogetherwhile MnO2 (8.19 g,
94.5 mmol) was added. The reaction mixture was heated at
reflux for 16 h, cooled briefly, then filtered through Celite, and
the solvent evaporated under reduced pressure. Recrystalliza-
tion from EtOAc/hexane (1 : 19) gave 1-(2-perfluorohexyl)
ethyl-1H-1,2,3-triazole-4-carbaldehyde 34 as a white powder
(7.39 g, 89 %), mp 85–878C. Found: C 29.81, H 1.36, N 9.48.
C11H6N3OF13 requires C 29.67, H 1.52, N 9.67 %). m/z (HR-MS
ESI) 973.1010 ([2M þ 2CH3OHþNa]þ, 100), 498.0448 ([M
þ CH3OHþNa]þ, 96 %). C11H6N3OF13 requires m/z 973.1029
([2M þ 2CH3OHþNa]þ), 498.0463 ([M þ CH3OHþNa]þ). nmax
(ATR)/cmꢁ1 3106, 3051, 2844, 2775, 2320, 2206, 2092, 1701,
1539, 1435, 1400, 1365, 1316, 1288, 1230, 1182, 1139, 1077,
1051, 1026, 983, 882, 828, 793, 760, 700. dH (400 MHz, CDCl3)
2.88 (tt, JH–F 17.8, J 7.2, 2H, H20), 4.78 (t, J 7.2, 2H, H10), 8.19
(s, 1H, H5), 10.1 (s, 1H, H100). dC (100 MHz, CDCl3) 31.7 (t,
JC–F 21.8, C20), 43.2 (t, JC–F 5.0, C10), 126.0 (C5), 148.1 (C4),
184.9 (C100). dF (376 MHz, CDCl3) ꢁ80.8 (tt, JF–F 9.7, JF–F 2.3,
General Method for Preparation of Secondary
Amines 39 and 44
Aldehyde 34 (1.0 mol equiv.) and the amine 36 or 42 (1.0 mol
equiv.) were dissolved in EtOH (150 mL) and the reaction
mixture was heated at reflux for 1 h. The reaction mixture was
then cooled to 08C and NaBH4 (1.0 mol equiv.) was added
portionwise while stirring. The reaction was allowed to warm to
rt and stirred for 16 h, then quenched with brine (150 mL), and
the resultant mixture was extracted with EtOAc (3 ꢀ 100 mL).
The combined organic layers were dried over MgSO4 and the
organic solvent was removed under reduced pressure. The crude
product was flash-chromatographed on reverse-phase fluorous
silica gel (MeOH) and then on silica gel (acetone/MeOH, 9 : 1),
and finally recrystallized from EtOAc/hexane (1 : 10).
(i) Aldehyde 34 (5.97 g, 13.5 mmol) and amine 36 (2.20 g,
13.5 mmol) gave N-(2-(2-(2-methoxyethoxy)ethoxy))-N-((1-(2-
perfluorohexyl)ethyl-1H-1,2,3-triazol-4-yl)methyl)ethanamine

J
D. V. Francis, J. B. Harper, and R. W. Read
39 as a pale white powder (3.82 g, 48 %), mp 36–388C. Found: C
36.34, H 3.80, N 9.22. C18H23N4O3F13 requires: C 36.62, H
3.93, N 9.49 %. m/z (HR-MS ESI) 1181.3171 ([2M þ H]þ, 84),
613.1431 ([M þ Na]þ, 100). C18H23N4O3F13 requires m/z
1181.3203 ([2M þ H]þ), 613.1460 ([M þ Na]þ). nmax (ATR)/
cmꢁ1 3276, 3118, 3069, 2998, 2886, 2837, 1557, 1456, 1366,
1326, 1230, 1185, 1143, 1092, 1026, 987, 940, 879, 853, 807,
771. dH (400 MHz, CDCl3) 2.27 (s, 1H, NH), 2.79 (tt, JH–F 18.1,
JH–H 7.3, 2H, H20000), 2.83 (t, J 5.1, 2H, H1), 3.35 (s, 3H, H50),
3.53 (m, 2H, H40), 3.61 (m, 8H, H2 and H10-H30), 3.93 (s, 2H,
H100), 4.65 (t, J 7.3, 2H, H10000), 7.58 (s, 1H, H5000). dC (100 MHz,
CDCl3) 32.0 (t, JC–F 21.8, C20000), 42.3 (t, JC–F 5.0, C10000), 44.7
(C100), 48.7 (C1), 59.1 (C50), 70.38, 70.41, 70.65 (C2 and C10-
C20), 70.59 (C30), 72.0 (C40), 122.4 (C5000), 147.3 (C4000). dF
(282 MHz, CDCl3) ꢁ80.8 (tt, JF–F 10.1, 1.9, 3F, CF3CF2),
ꢁ114.2 (m, 2F), ꢁ121.8 (m, 2F), ꢁ122.8 (m, 2F), ꢁ123.5 (m,
2F), ꢁ126.1 (m, 2F).
1145, 1122, 1047, 948, 850, 809, 781, 746, 736, 708, 698. dH
(300 MHz, CDCl3) 1.22 (t, J 7.1, 3H, H20), 1.79 (tt, J 14.4, 7.2,
2H, H2), 2.29 (t, J 7.2, 2H, H3), 2.51 (t, J 7.2, 2H, H1), 2.66 (t, J
5.7, 2H, H100), 2.81 (tt, JH–F 18.1, JH–H 7.6, 2H, H200000), 3.34 (s,
3H, H700), 3.51 (m, 2H, H600), 3.56 (m, 2H, H200), 3.57 (m, 2H,
H300 or H400), 3.61 (m, 2H, H300 or H400), 3.63 (m, 2H, H500) 3.85
(s, 2H, H1000), 4.06 (qr, J 7.1, 2H, H10), 4.65 (t, J 7.6, 2H, H100000),
7.67 (s, 1H, H50000). dC (75 MHz, CDCl3) 14.3 (C20), 22.6 (C2),
31.9 (t, JC–F 21.7, C200000), 32.0 (C3), 42.2 (t, JC–F 5.0, C100000),
49.2 (C1000), 53.0 (C100), 53.5 (C1), 59.0 (C700), 60.3 (C10), 69.9
(C200), 70.4, 70.5 (C300–C400), 70.7 (C500), 72.0 (C600), 123.7
(C50000), 145.7 (C40000), 173.7 (C4). dF (282 MHz, CDCl3) ꢁ80.8
(tt, JF–F 9.9, 2.2, 3F, CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.8 (m, 2F),
ꢁ122.8 (m, 2F), ꢁ123.5 (m, 2F), ꢁ126.1 (m, 2F).
(ii) Amine 39 (0.50 g, 0.847 mmol) and 1,2:3,4-di-O-iso-
propylidene-a-D-galactos-6-yl triflate 46 (0.365 g, 0.932 mmol)
gave
N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-N-((1-(2-per-
(ii) Aldehyde 34 (1.81 g, 4.08 mmol) and triazolylmethyl
amine 42 (1.00 g, 4.10 mmol) gave N-(1-(2-(2-(2-methoxy-
ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-N-(1-(2-
perfluorohexyl)ethyl)-1H-1,2,3-triazol-4-yl)amine 44 as a pale
white powder (0.90 g, 33 %), mp 53–558C. Found: C 37.51, H
4.11, N 14.53. C21H26N7O3F13 requires: C 37.56, H 3.90, N
14.60 %. m/z (HR-MS ESI) 1343.3831 ([2M þ H]þ, 79),
694.1758 ([M þ Na]þ, 100 %). C21H26N7O3F13 requires m/z
1343.3857 ([2M þ H]þ), 694.1787 ([M þ Na]þ). nmax (ATR)/
cmꢁ1 3306, 3148, 3109, 3069, 2894, 2815, 1558, 1459, 1397,
1365, 1319, 1288, 1181, 1136, 1101, 1033, 988, 950, 918, 851,
813, 766. dH (400 MHz, CDCl3) 2.39 (s, 1H, NH), 2.80 (tt, JH–F
18.0, JH–H 7.5, 2H, H20), 3.35 (s, 3H, H70000), 3.52 (m, 2H, H60000),
3.59 (m, 2H, H50000), 3.61 (m, 4H, H30000–H40000), 3.85 (t, J 5.2, 2H,
H20000), 3.93 (s, 2H, H100 or H200), 3.94 (s, 2H, H100 or H200), 4.52
(t, J 5.2, 2H, H10000), 4.65 (t, J 7.5, 2H, H10), 7.61 (s, 1H, H5), 7.70
(s, 1H, H5000). dC (100 MHz, CDCl3) 32.0 (t, JC–F 21.9, C20), 42.3
(t, JC–F 5.0, C10), 43.7 (C100 or C200), 43.8 (C100 or C200), 50.3
(C10000), 59.1 (C70000), 69.6 (C20000), 70.6 (C50000), 70.7 (C30000 and
C40000), 72.0 (C60000), 122.7 (C5), 123.3 (C5000), 145.8 (C4000),
146.7 (C4). dF (282 MHz, CDCl3) ꢁ80.7 (tt, JF–F 10.1, 1.7, 3F,
CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.8 (m, 2F), ꢁ122.8 (m, 2F),
ꢁ123.4 (m, 2F), ꢁ126.1 (m, 2F).
fluorohexyl)ethyl-1H-1,2,3-triazol-4-yl)methyl)-6-amino-1,2:3,
4-di-O-isopropylidene-a-D-galactose 48 as a colourless oil
(0.43 g, 61 %). m/z (HR-MS ESI) 833.2783 ([M þ H]þ, 100 %.
C30H41N4O8F13 requires m/z 833.2795 ([M þ H]þ). nmax (film)/
cmꢁ1 3137, 2987, 2897, 1644, 1556, 1457, 1383, 1351, 1241,
1002, 918, 902, 852, 809, 771, 746, 736, 708, 698. dH (300 MHz,
CDCl3) 1.31 (s, 6H, H100 and H10000), 1.41 (s, 3H, H2000), 1.52
(s, 3H, H700A), ,2.72 (m, 2H, H100000), ,2.79 (m, 2H, H6),
,2.80 (m, 2H, H100000000), 3.35 (s, 3H, H700000), 3.52 (m, 2H,
H600000), 3.65 (m, 8H, H200000-H500000), 3.97 (s, 2H, H1000000), 4.04
(m, 1H, H5), 4.22 (dd, J 7.9, 1.7, 1H, H4), 4.28 (dd, J 5.1, 2.3,
1H, H2), 4.57 (dd, J 7.9, 2.3, 1H, H3), 4.64 (t, J 7.6, 2H,
H200000000), 5.53 (d, J 5.1, 1H, H1), 7.73 (s, 1H, H50000000). dC
(75 MHz, CDCl3) 24.6 (C10000), 25.0 (C100), 26.1 (C2000), 26.2
(C20), 32.0 (t, JC–F 21.5, C200000000), 42.2 (t, JC–F 5.3, C100000000),
49.3 (C1000000), 53.5 (C100000), 54.2 (C6), 59.1 (C700000), 65.9 (C5),
70.3 (C500000), 70.56, 70.74 (C200000–C400000), 70.65 (C2), 71.0 (C3),
72.1 (C600000), 72.3 (C4), 96.8 (C1), 108.6 (C10), 109.2 (C1000),
124.0 (C50000000), 145.9 (C40000000). dF (282 MHz, CDCl3) ꢁ80.8 (tt,
JF–F 9.7, 1.8, 3F, CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.8 (m, 2F),
ꢁ122.8 (m, 2F), ꢁ123.5 (m, 2F), ꢁ126.1 (m, 2F).
(iii) Amine 44 (0.50 g, 0.745 mmol) and ethyl 4-bromo-
butanoate 45 (0.160 g, 0.820 mmol) gave ethyl N-(((1-(2-(2-
methoxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-N-
(((1-(2-perfluorohexyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)
aminobutanoate 52 as a pale white powder (0.15 g, 26 %) mp
38–408C. Found: C 41.26, H 4.70, N 12.35. C27H36N7O5F13
requires: C 41.28, H 4.62, N 12.48 %. m/z (HR-MS ESI)
808.2432 ([M þ Na]þ, 100). C27H36N7O5F13 requires m/z
808.2468 ([M þ Na]þ). nmax (ATR)/cmꢁ1 3117, 3073, 2929,
2879, 2821, 1726, 1643, 1553, 1458, 1434, 1376, 1343, 1321,
1280, 1224, 1179, 1144, 1096, 1050, 962, 931, 885, 836, 818,
762, 745. dH (400 MHz, CDCl3) 1.22 (t, J 7.2, 3H, H20), 1.91 (m,
2H, H2), 2.32 (t, J 7.2, 2H, H3), 2.53 (m, 2H, H1), 2.83 (tt, JH–F
18.0, JH–H 7.6, 2H, H20000000), 3.35 (s, 3H, H70000), 3.52 (m, 2H,
H60000), 3.60 (m, 2H, H50000), 3.62 (m, 4H, H30000–H40000), 3.76
(s, 2H, H100 or H100000), 3.78 (m, 2H, H100 or H100000), 3.88 (t, J 5.2,
2H, H20000), 4.07 (q, J 7.2, 2H, H10), 4.54 (t, J 5.1, 2H, H10000),
4.68 (t, J 7.6, 2H, H10000000), 7.78 (m, 2H, H5000 or H5000000).
dC (100 MHz, CDCl3) 14.3 (C20), 22.5 (C2), 31.9 (t, JC–F 21.7,
C20000000), 32.0 (C3), 42.4 (t, JC–F 4.0, C10000000), 47.5, 47.7 (C100
and C100000), 50.4 (C10000), 52.5 (C1), 59.1 (C70000), 60.4 (C10), 69.6
(C20000), 70.65 (C30000–C40000), 70.70 (C50000), 72.0 (C60000), 124.5
(C5000 and C5000000), ,144.7 (C4000 and C4000000), 173.7 (C4).
(iv) Amine 44 (0.50 g, 0.745 mmol) and 1,2:3,4-di-O-
isopropylidene-a-D-galactos-6-yl triflate 46 (0.320 g, 0.820 mmol)
General Method for the Alkylation of Triazolylmethyl
Amines 39 and 44
The appropriate amine (1.0 mol equiv.), Et3N (1.1mol equiv.),
and the specified alkylating agent (either 45 or 46, 1.1 mol
equiv.) were dissolved in MeCN (20 mL). The reaction mixture
was heated at reflux for 16 h, then quenched with saturated
aqueous NaHCO3 (20 mL), and the reaction mixture was
extracted with EtOAc (3 ꢀ 20 mL). The combined organic layers
were washed with brine (2 ꢀ 20 mL), dried over MgSO4, and
the organic solvent removed under reduced pressure. The crude
product was flash-chromatographed on reverse-phase fluorous
silica gel (MeOH), then on silica gel (MeOH/EtOAc, 3 : 97).
(i) Amine 39 (0.50 g, 0.847 mmol) and ethyl 4-bromo-
butanoate 45 (0.182 g, 0.932 mmol) gave ethyl N-(2-(2-(2-
methoxyethoxy)ethoxy)ethyl)-N-(((1-(2-perfluorohexyl)ethyl)-
1H-1,2,3-triazol-4-yl)methyl)aminobutanoate 47 as a yellow oil
(0.39 g, 65 %). Found:
C
40.76,
H
4.56,
N
8.26.
C24H33N4O5F13ꢂ0.5H2O requires: C 40.40, H 4.80, N 7.85 %.
m/z (HR-MS ESI) 705.2320 ([M þ H]þ, 100 %).
C24H33N4O5F13 requires m/z 705.2322 ([M þ H]þ). nmax
(film)/cmꢁ1 3137, 2878, 1732, 1461, 1368, 1351, 1240, 1204,

Fluorous Triazolylmethylamines for Surfactant Applications
K
gave N-(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl-1H-1,2,3-triazol-
4-yl)methyl)-N-((1-(2-perfluorohexyl)ethyl-1H-1,2,3-triazol-4-yl)
methyl)-6-amino-1,2 : 3,4-di-O-isopropylidene-a-D-galactose 53
as a colourless gum (0.27 g, 40 %). m/z (HR-MS ESI) 914.3091
([M þ H]þ, 100%). C33H44N7O8F13 requires m/z 914.3122 ([M
þ H]þ). nmax (film)/cmꢁ1 3137, 2988, 2936, 2362, 1699, 1644,
1583, 1557, 1457, 1383, 1240, 1145, 1070, 1001, 919, 903, 851,
809, 772, 746, 736, 708. dH (600 MHz, CDCl3) 1.30 (m, 3H, H20
or H2000), 1.32 (m, 3H, H2000 or H2000), 1.40 (m, 3H, H10000), 1.54
(m, 3H, H100), 2.77 (m, 2H, H6), 2.81 (tt, JH–F 16.7, JH–H 7.6, 2H,
H20000000000), 3.35 (s, 3H, H70000000), 3.51 (m, 2H, H60000000), 3.60 (m,
2H, H50000000), 3.61 (m, 4H, H30000000–H40000000), 3.87 (t, J 5.2, 2H,
H20000000), 4.21 (dd, J ,7.8, 1.0, 1H, H4), 4.30 (dd, J 5.0, 2.0, 1H,
H2), 4.52 (t, J 5.2, 2H, H10000000), 4.58 (dd, J 7.8, 2.0, 1H, H3), 4.65
(t, J 7.6, 2H, H10000000000), 5.56 (d, J 5.0, 1H, H1), 7.79 (s, 1H,
H50000000000), 7.81 (s, 1H, H5000000000). dC (150 MHz, CDCl3)
24.5 (C100 or C10000), 25.0 (C100 or C10000), 26.1 (C2000), 26.2
(C20), 32.0 (t, JC–F 21.7, C20000000000), 42.3 (t, JC–F 5.7, C10000000000),
50.3 (C10000000), 53.2 (C6), 59.1 (C70000000), 69.6 (C20000000), 70.61
(C2), 70.65 (C30000000 or C40000000), 70.66 (C50000000), 70.74 (C30000000 or
C40000000), 71.0 (C3), 72.0 (C60000000), 72.3 (C4), 96.8 (C1), 108.6
(C10), 109.2 (C1000), 124.4 (C5000000000), 124.8 (C5000000), 143.7
(C4000000), 144.6 (C4000000000). dF (376 MHz, CDCl3) ꢁ80.7 (tt, JF–F
9.8, 1.8, 3F, CF3CF2), ꢁ114.1 (m, 2F), ꢁ121.8 (m, 2F), ꢁ122.8
(m, 2F), ꢁ123.4 (m, 2F), ꢁ126.1 (m, 2F).
2.3, 3F, CF3CF2), ꢁ114.2 (m, 2F), ꢁ121.8 (m, 2F), ꢁ122.8 (m,
2F), ꢁ123.4 (m, 2F), ꢁ126.1 (m, 2F).
Subsequent chromatographic fractions yielded what was
thought to be N-(2-(2-(2-methoxyethoxy)ethoxy))-N-((1-(2-
perfluorohexyl)ethyl-1H-1,2,3-triazol-4-yl)methyl)ethanamine
hydrochloride 51 as a solid (0.12 g, 23 %). Found: C 34.03, H
3.81, N 8.60. C18H24N4O3ClF13 requires: C 34.49, H 3.86, N
8.94 %. m/z (HR-MS ESI) 591.1632. C18H24N4O3F13 requires
m/z 591.1641. dH (400 MHz, CDCl3) 8.55 (s, 1H). dH (400 MHz,
CDCl3) 2.82 (br m, 2H, CF2CH2CH2N). 3.16 (br s, 2H,
NCH2CH2O), 3.36 (s, 3H, OCH3), 3.53 (s, 2H, CH2OCH3),
3.63 (s, 2H), 3.66 (s, 2H), 3.69 (s, 2H), 3.91 (s, 2H, NCH2CH2O),
4.44 (s, 2H, 4-CH2N), 4.71 (s, 2H, CF2CH2CH2N), 8.52 (s, 1H,
triazole-H4), 9.79 (br s, 2H, R2NHþ2 ). dC (100 MHz, CDCl3)
31.8 (t, J ,20, CF2CH2CH2N), 41.9 (4-CH2N), 42.8 (t, J ,5,
CF2CH2CH2N), 45.8 (NCH2CH2O), 59.1 (OCH3), 65.7
(NCH2CH2O), 70.08, 70.16, 70.21, 71.6 (CH2OCH3), 127.3
(C4), 138.4 (C5).
Supplementary Material
Details of method development and copies of spectra for all new
compounds are available on the Journal’s website.
Acknowledgements
This research was generously supported through small grant funding from
the University of New South Wales. The authors thank Mr Ahmed Ahmed
for the generous provision of triflate 46.
Acylation of Bis-(triazolylmethyl)amine 39 with
1-Adamantoyl Chloride 49
1-Adamantanecarboxylic acid (0.38 g, 2.11 mmol) and SOCl2
(1.0 mL) were heated at reflux for 3 h. The excess SOCl2 was
removed by distillation under reduced pressure to give acid
chloride 49, which was dissolved in MeCN (20 mL) along with
the amine 39 (0.50 g, 0.847 mmol), and Et3N (0.119 mL,
0.931 mmol). The reaction mixture was heated at reflux for 16 h,
then quenched with saturated aqueous NaHCO3 (20 mL) and the
resulting mixture was extracted with EtOAc (3 ꢀ 20 mL). The
combined organic layers were washed with brine (2 ꢀ 20 mL),
dried over MgSO4, and the organic solvent removed under
reduced pressure. Flash chromatography on reverse-phase
fluorous silica gel (MeOH), followed by flash chromatography
on silica gel (acetone/hexane, 15 : 85) afforded (3r,5r,7r)-N-(2-
(2-(2-methoxyethoxy)ethoxy)ethyl)-N-((1-perfluorohexylethyl-
1H-1,2,3-triazol-4-yl)methyl)adamantane-1-carboxamide 50 as
a yellow oil (0.30 g, 47 %). Found: C 46.66, H 4.85, N 7.39.
C29H37N4O4F13 requires: C 46.28, H 4.96, N 7.44 %. m/z (HR-
MS ESI) 1527.5097 ([2M þ Na]þ, 60), 753.2678 ([M þ H]þ,
100 %). C29H37N4O4F13 requires m/z 1527.5112 ([2M þ Na]þ),
753.2685 ([M þ H]þ). nmax (film)/cmꢁ1 3136, 2908, 2360, 2342,
1621, 1551, 1455, 1406, 1366, 1243, 1145, 990, 939, 850, 810,
780, 746, 735, 708, 698. dH (400 MHz, CDCl3) 1.69 (m, 6H, H4,
H6 and H100), 1.97 (m, 6H, H2, H8 and H10), 2.01 (m, 3H, H3,
H5 and H7), 2.80 (tt, JH–F 18.0, J 7.5, 2H, H20000000), 3.35 (s, 3H,
H70000), 3.52 (m, 2H, H60000), 3.53 (m, 2H, H50000), 3.61 (m, 4H,
H30000–H40000), 3.64 (t, J 5.2, 2H, H10000, H20000 or H100000), 3.72 (m,
2H, H10000, H20000 or H100000), 4.63 (t, J 7.5, 2H, H10000000), 4.68 (m,
2H, H10000, H20000 or H100000), 7.61 (s, 1H, H5000000). dC (100 MHz,
CDCl3) 28.6 (C3, C5 and C7), 31.8 (t, JC–F 21.7, C20000000), 36.6
(C4, C6 and C100), 39.3 (C2, C8 and C10), 42.4 (t, JC–F 5.6,
C10000000), 44.6 (C10000, C20000 or C100000), 48.2 (C10000, C20000 or
C100000), 59.1 (C70000), 69.5 (C10000, C20000 or C100000), 70.64 (C50000),
70.67, 70.69 (C30000–C40000), 72.0 (C60000), 124.0 (C5000000), 146.0
(C4000000), 177.4 (C1000). dF (376 MHz, CDCl3) ꢁ80.7 (tt, JF–F 9.9,
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