Novel generation ponytails in fluorous chemistry: Syntheses of primary, secondary, and tertiary (nonafluoro-tert-butyloxy)ethyl amines

Article abstract of DOI:10.1016/j.jfluchem.2006.06.020

(Nonafluoro-tert-butyloxy)ethyl tosylate 4 was prepared in 65% yield from nonafluoro-tert-butanol 1 using commercially available reagents. Further reaction of 4 with HNR¹R² (R¹ = R² = H, CH₃; R^1<

Full text of DOI:10.1016/j.jfluchem.2006.06.020

Journal of Fluorine Chemistry 127 (2006) 1496–1504
www.elsevier.com/locate/fluor
Novel generation ponytails in fluorous chemistry:
Syntheses of primary, secondary, and tertiary
(nonafluoro-tert-butyloxy)ethyl amines
´ ´ ´ ´
Denes Szabo, Janos Mohl, Ana-Maria Balint,
*
´ ´
Andrea Bodor, Jozsef Rabai
¨ ¨
´
Institute of Chemistry, Eotvos Lorand University, P.O. Box 32, H-1518 Budapest 112, Hungary
Received 13 March 2006; received in revised form 27 June 2006; accepted 28 June 2006
Available online 4 July 2006
Dedicated to Dr. Frank J. Pavlik for his pioneer works.
Abstract
(Nonafluoro-tert-butyloxy)ethyl tosylate 4 was prepared in 65% yield from nonafluoro-tert-butanol 1 using commercially available reagents.
Further reaction of 4 with HNR1R2 (R1 = R2 = H, CH3; R1 = H, R2 = CH3, (CH2)3C8F17, CH2CH2OC(CF3)3) affords the appropriate
(CF3)3COCH2CH2NR1R2 amines in 20–69% yields. Improved overall yields of [(CF3)3COCH2CH2]3ÀnNRn to 1 were obtained by the reaction
of (CF3)3CONa 2 and (XCH2CH2)3ÀnNRn (X = Cl, n = 0, 1, 2, R = CH3; X = CH3SO2O, n = 1, R = CH3SO2) nitrogen mustards and a similar
reactive b-substituted ethyl amine. The title amines are mobile colorless liquids and volatile with steam. The bulky fluorous ponytail
(CF3)3CO(CH2)2 displays high acidic stability and increases fluorous character almost as much as the classical straight-chain C8F17(CH2)3
ponytail.
# 2006 Elsevier B.V. All rights reserved.
Keywords: Amines; Ethers; Fluorous partition coefficient; Steam-distillation; Williamson-synthesis
1. Introduction
A general concept for solution phase mixture synthesis by
separation tagging has been introduced and put into practice
with homologous fluorous tags, such as the FPMB {–CH2C6H4–
p-O(CH2)3CnF2n+1, n = 2, 4, 6, 8} protecting groups [5]. In a
recent improvement of solution phase mixture synthesis
oligoethylene glycol (OEG; (OCH2CH2)nOCH3) and fluorous
tags are used simultaneously; where the isolation of the final
products is achieved by double demixing with a separate
demixing process that targets each tag class. Consequently, an
access to four tags in each of the OEG and fluorous series,
allowed the easy separation of 16 compounds [5].
Fluorous chemistry provides efficient approaches for the
synthesis of organic molecules coupled with engineered
product isolation techniques [1]. The number of fluorous
processes is still growing and some of these have become
indispensable means of contemporary synthetic chemistry [2].
The ultimate cause of the success of the main streams of
fluorous chemistry – fluorous biphasic catalysis, fluorous
synthesis and fluorous mixture synthesis – can be identified at
the molecular level with the presence of perfluoroalkyl groups
or fluorous ponytails [3]. These structural elements encode the
fluorous nature of the molecules that bearing them and enable
performing effective separations at the macroscopic level using
fluorous techniques including fluorous liquid–liquid extractions
and filtration or chromatography over fluorous silica gel [4].
To offer alternative F-ponytails (e.g. branched perfluor-
oalkyl-chains) for various applications, we aimed to synthesize
fluorophilic amines that have wide fluidity ranges. Such
reagents are expected to display effective fluorous liquid–
organic liquid separation at lower temperatures, while forming
homogeneous systems at higher.
We selected perfluoro-tert-butyl alcohol [(CF3)3COH, 1]
for these studies; it has become a commercially available
reagent after a long period of being a curiosity [6]. Some
* Corresponding author. Tel.: +36 1 2090555; fax: +36 1 2090602.
´
E-mail address: rabai@elte.hu (J. Rabai).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.06.020

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1497
Table 1
perfluoro-tert-alcohols with longer chains are also known, and
could have a role in fluorous applications [7].
Some ethers and esters disclosed in US Patent 3,385,904
Compound
Chemical formula
Comments
2. Results and discussion
1
2
3
7
8
(CF3)3COH
Bp 48/760, pKa = 5.5
Soluble in ether
Bp 125/740
(CF3)3CONa
(CF3)3COCH2CH2OH
(CF3)3COC(O)CH CH2
(CF3)3COCH2CH2OC(O)CH CH2
(CF3)3COCH2CO2C2H5
(CF3)3COCH2CO2H
The synthesis and isolation of some (perfluoro-tert-butylox-
y)ethyl amines (I-a–g) are described in Scheme 1. These
compounds are designed to expand the existing inventory of
fluorous amines [8], which include only linear perfluoroalkyl-
chains in their ponytails [3b]. The precursor perfluoro-tert-butyl
alcohol 1 provides ‘‘three-at-one-shoot’’ of the superfluorophilic
CF3-groups for their introduction to target molecules and serves
as a module for a ‘‘war-hammer’’ type of fluorous ponytail.
We first synthesized a bulky fluorous alkylating reagent, 2-
(perfluoro-tert-butyloxy)ethyl tosylate 4 in 65% yield using a
three-step procedure (Scheme 2, Table 1). Alcohol 1 was
converted to its sodium salt 2 in quantitative yield by simple
titration with aqueous NaOH, followed by solvent evaporation.
Then 2 was reacted with 2-bromoethanol in DMF at 120 8C for
2 h. The fluorous ethanol 3 formed was isolated by phasing out
with water and purified by distillation. Consecutive reaction
with p-toluenesulfonyl chloride in pyridine followed by the
usual workup and crystallization from petroleum ether gave 4
as white crystalline product. Then tosylate 4 was applied for the
preparation of amine I-a using a Gabriel-synthesis with the
Ing–Manske protocol [9]. Compound 4 was reacted with
potassium phthalimide in DMF and the alkylated product 5
isolated by an CH2Cl2–water partition. Consecutive boiling
with hydrazine hydrate in methanol and with 6N HCl gave a
mixture of I-a*HCl and phthalylhydrazide. Steam-distillation
of the mixture made alkaline by NaOH afforded a two-phase
distillate (cf. Section 4), the lower yields amine I-a.
Bp 99–101/760
Bp 35/1
9
Bp 140–145/750
Mp 85–87
10
11
12
13
(CF3)3CO(CH2)9CH CH2
(CF3)3COSO2CF3
Bp 56/0.5
Bp 91/760
(CF3)3COCH2CH(OH)CH2OH
Bp 60–65/1
the Ph3P/DIAD reagent pair. We note, that 5 and I-a have been
prepared earlier using a similar procedure, but with chromato-
graphic product isolation (Scheme 3) [11]. The (CF3)3COCH2-
CH2ONH2 analogue has been made by substituting PhthNO-
CH2CH2OH for 6 (cf. Scheme 3) [12].
Although, the linear synthesis of I-a is less effective than the
Mitsunobu reaction, with 16% and 37% overall yields to 1,
respectively, it has benefits by affording fluorous reagents
(CF3)3CONa (2), (CF3)3COCH2CH2OH (3) and (CF3)3COCH2-
CH2OTs (4) in good yields and high purity.
The first synthesis of 1 involves the oxidation of
perfluoroisobutene to an oxirane and its consecutive reaction
with anhydrous hydrogen fluoride under harsh conditions
(250 8C, 64 h, pressure). The addition of SbF5 facilitates the
latter ring cleavage reaction. Compound 2 was obtained by the
reaction of 1 and sodium metal in ether as a clear solution or
white powder after filtration and evaporation, respectively.
When 2 and ethylene bromohydrine heated at reflux in
methylethyl ketone for 88 h an 85% yield of 3 was obtained by
distillation. Most of the perfluoro-tert-butyl ethers described
here are volatile liquids (Table 1) [6f].
As an extension of our study on the reactivity of fluorous
alcohols in Mitsunobu reactions [10], we synthesized 5 by
condensation of N-(2-hydroxyethyl)phthalimide 6 and 1 with
Scheme 1. Primary, secondary and tertiary amines with (perfluoro-tert-butyloxy)ethyl ponytails.
Scheme 2. Gabriel-synthesis of (F-tert-butyloxy)ethyl amine (I-a) using 4 as a F-tagging reagent.

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1498
Scheme 3. Mitsunobu synthesis of phthalimide 5 from (CF3)3COH (1) and its deprotection to primary amine I-a.
We thought that tosylate 4 could provide an easy access to
We applied 14, an N-protected bis-alkylating reagent
accessible by the reaction of diethanol amine and CH3SO2Cl
in pyridine or CH2Cl2/N(C2H5)3 system [13], for an improved
synthesis of I-c (Scheme 5).
novel fluorous amines upon aminolysis (Scheme 4). Thus I-a, I-
b and I-e was obtained in good yields by the reaction of 4 in a
pressure vessel with a large excess of ammonia, methyl amine
or dimethyl amine, respectively, at ambient or elevated
temperatures. These amines with one tail were isolated by
steam-distillation since they are immiscible with water and
displaying high volatility.
The reaction of 14 and 20% excess of 2 in DMF at 100 8C
resulted in the formation of the corresponding N,N-bis[(per-
fluoro-tert-butyloxy)ethyl]methane sulfonamide 15 in 75%
yield. Sulfonamide 15 then was hydrolysed to methanesulfonic
acid and I-c by heating with an excess of 96% H2SO4 at 100 8C
for 30 h. It must be emphasized, that cleavage reaction
selectively occurs at the SO2–N bonds without damaging the
(perfluoro-tert-butyloxy)ethyl groups. This is an indication of
the unique inertness of the (CF3)3COCH2CH2-structural
fragment.
The reaction of 2 equiv. of C8F17(CH2)3NH2 with 4 at
ꢀ100–110 8C furnished I-d in 60% yield, while I-a under
similar conditions afforded a difficult to separate mixture of I-
a:I-c:I-g = 30:60:10 as determined by GC. Partitions between
FC-72/CH3OH, followed by fractional distillation of the
combined fluorous phases gave I-c in 20% yield with 95%
GC purity (Scheme 4).
The reaction of sodium nonafluoro-tert-butoxide 2 and b-
chloroalkylamine hydrochlorides 16, 17 and 18 results in the
formation of the appropriate ether linkages and this method
furnishes amines I-e–g, respectively, in a one step synthesis
(Scheme 6).
Due to the latter difficulties, we introduced an alternative
strategy for the synthesis of (perfluoro-tert-butyloxy)ethyl
amines, where the target compounds are assembled using O-
alkylation steps (Williamson-synthesis). This strategy allows
the late introduction of fluorous segments, thus it could result in
a higher overall yield.
These syntheses offer better fluorine atom economy due to
the late introduction of the fluorous alkoxy-groups at the
Scheme 4. Aminolysis reactions of (CF3)3COCH2CH2OTs (4).
Scheme 5. Synthesis of I-c with late introduction of fluorous ponytails.

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1499
Table 2
Fluorophilicity and fluorousness values for selected amines
a
Entry
Compound
ln P
%fness
1
2
(CF3)3CO(CH2)2NH2
À0.14
À0.083
1.82
À3.3
À1.8
24
(CF3)3CO(CH2)2NH(CH3)
[(CF3)3CO(CH2)2]2NH
(CF3)3CO(CH2)2NH(CH2)3Rf8
(CF3)3CO(CH2)2N(CH3)2
[(CF3)3CO(CH2)2]2NCH3
[(CF3)3CO(CH2)2]3N
3
4
2.69
29
5
0.336
2.03
6.1
25
6
7
3.62
32
8
Rf8(CH2)3NH2
0.846b
0.542b
0.278b
1.07b
0.875b
0.708c
1.98c
4.08c
3.32b
2.97b
2.59b
1.53b
1.37b
3.63b
>5.81b
>5.81b
5.29b
14
b
b
9
Rf8(CH2)4NH2
8.6
4.2
21
b
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Rf8(CH2)5NH2
Rf7CH2NH(CH3)b
Rf8(CH2)3NH(CH3)b
[Rf4(CH2)3]2NHc
[Rf6(CH2)3]2NHc
[Rf10(CH2)3]2NHc
[Rf8(CH2)3]2NHb
[Rf8(CH2)4]2NHb
[Rf8(CH2)5]2NHb
14
10
21
31
30
25
Scheme 6. One step synthesis of (nonafluoro-tert-butyloxy)ethyl amines.
21
b
Rf7CH2N(CH3)2
27
b
Rf8(CH2)3N(CH3)2
20
b
[Rf8(CH2)3]2NCH3
31
expense of using commercially available but toxic nitrogen
mustard like precursors [14].
[Rf8(CH2)3]3Nb
[Rf8(CH2)4]3Nb
[Rf8(CH2)5]3Nb
>35
>33
29
Amines I-a–g were characterized by NMR (1H, 13C, 19F),
and IR spectroscopy, as summarized in Section 4. They are
liquid, volatile with steam and soluble in a broad spectrum of
non-fluorous solvents as well as CF3C6F11 [perfluoro(methyl-
cyclohexane)].
a
%fness(i) = 24.4 Â fspec(i) = 24.4 Â ([Vm(CF3C6F11)]/[Vm(i)]) Â ln PFBS
.
b
c
cf. Ref. [4b], pp. 74–75.
cf. Ref. [7f].
We sought to quantify the fluorous-phase affinities of the
compounds in Scheme 1. Thus, the CF3C6F11/toluene partition
coefficients, P, were measured by GC as described in Section 4.
Results are displayed in two different terms, such as ln P and
fluorousness together with many previously reported values
(Table 2). The actual figures were calculated from experimental
partition coefficients as described earlier [10,15].
group on the increase of fluorousness parameter can be ascribed
to both volume and cohesion effects [15].
3. Conclusions
(1) The present work demonstrated for the first time, that
nonafluoro-tert-butanol is a suitable precursor for the
preparation of fluorophilic amines. The measured fluor-
ofilicity and calculated fluorousness values indicate that
nonafluoro-tert-butyloxyethyl group could be a very
effective substitute for longer perfluoroalkyl groups.
(2) The introduction of novel ponytails could result in the
substitution of perfluorooctyl derivatives and the elimina-
tion of environmental issues, which are associated with
perfluorooctanoic acid, a potential decomposition product
of CF3(CF2)7R compounds [16].
Unlike fluorophilicity, which in principle has no upper limit,
the fluorousness parameter does have an upper limit, since it is a
term normalized to molar volume. All trends in changes of
these descriptors with a compound’s structure follow pre-
dictable rules [15].
Firstly, fluorophilicities increase as the length of the Rfn
segments increases (entries 13–16). Secondly, fluorophilicities
decrease, as the length of the methylene spacers increases
(entries 8, 9, 10; 11, 12; and 19, 20). Third, amines with a single
fluorous segment are not very fluorophilic, some of them are
slightly organophilic (entries 1 and 2), but the sequential
removal of the hydrogen-bond forming N–H groups by
methylation increases their fluorophilicity and fluorousness
values (entries 1, 2, 5; 8, 12, 20; and 11, 19).
4. Experimental
4.1. General description of methods and materials
Our data establish furthermore, that fluorousness values
decrease in the order of [Rf8(CH2)3]3N, 35% > [(CF3)3CO-
(CH2)2]3N, 32% > [Rf8(CH2)3]2NCH3, 31% ꢁ [Rf10(CH2)3]2-
NH, 31% > [Rf8(CH2)3]2NH, 30% > (CF3)3CO(CH2)2NH-
(CH2)3Rf8, 29% ꢁ [Rf8(CH2)5]3N, 29% > Rf7CH2N(CH3)2,
Nonafluoro-tert-butanol, FC-72 (mix of perfluorohexanes),
and perfluoro(methylcyclohexane) were purchased from
Fluorochem, while amine C8F17(CH2)3NH2 was prepared as
reported [8b]. The other reagents and solvents were Aldrich or
Fluka products. Fourier transformed infrared spectra were
recorded neat, as a film, or KBr disc as indicated, on a Bruker
Equinox FTIR spectrophotometer, nmax in cmÀ1. The bands are
characterized as broad (br), strong (s), medium (m) or weak
27% > [Rf8(CH2)4]2NH,
25% ꢁ [(CF3)3CO(CH2)2]2NCH3,
25% > [(CF3)3CO(CH2)2]2NH, 24% > [Rf8(CH2)5]2NH, 21%
ꢁ [Rf6(CH2)3]2NH, 21% ꢁ Rf7CH2NH(CH3), 21% and >
Rf8(CH2)3N(CH3)2, 20%. The high efficacy of the (CF3)3CO-

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1500
(w). 1H NMR, 13C NMR and 19F NMR spectra were recorded
on Bruker Avance 250 and DRX500 spectrometers using 5 mm
IR (oil film): 3363 (w), 1256 (vs), 1164 (s), 972 (s) cmÀ1. 1H
NMR (CDCl3): d = 4.14 (2H, t, 3JHH = 4.4 Hz, C–O–CH2), 3.84
inverse H/13C/31P/19F and H/13C/15N probe heads at room
temperature, respectively. The ‘inverse gated’ and ‘jmod’
proton decoupling sequence was applied for 13C{1H} and
19F{1H} measurements. 1H–1H COSY, 1H–13C HSQC, 1H–13C
HMBC correlation experiments were also applied in some
cases. Data were expressed as chemical shifts in ppm relative to
residual chloroform (1H d 7.27), CDCl3 (13C d 77.0) or an
external standard for 19F (CFCl3, d = 0) on the d scale. Coupling
constants J were given in Hz. Melting points were determined
on a Boetius micromelting point apparatus and are uncorrected.
All reaction steps were monitored by gas chromatography
(Hewlett-Packard 5890 Series II, PONA [crosslinked methyl-
silicone gum] 50 m  0.2 mm  0.5 mm column, H2 carrier
gas, FID detection).
(2H, t, JHH = 4.4 Hz, CH2–OH), 2.72 (1H, broad, OH). 13C
1
1
3
1
NMR (CDCl3): d = 120.6 (3C, q, JCF = 292 Hz, CF3), 79.9
(1C, m, (CF3)3C), 71.5 (1C, s, C–O–CH2), 61.6 (1C, s, CH2–
OH). 19F NMR (CDCl3): d = À71.0 (9F, s, 3CF3).
4.4. 2-[1,1-Bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]ethyl-4-toluenesulfonate (4)
p-Toluenesulfonyl chloride (1.87 g, 9.81 mmol) was added
in portions to a stirred solution of perfluoro-tert-butyloxyethyl
alcohol, 3 (2.50 g, 8.93 mmol) in absolute pyridine (2.9 ml) at
0 8C, then it was allowed to warm to r.t. and stirred for 3 h. It
was poured onto a mixture of ice (15 g) and 12 M HCl (5 ml).
The precipitate formed was filtered, washed with water and
dried in vacuum over P2O5. GC purity of the crude product:
98.0%. Recrystallization from petroleum ether afforded 3.33 g
(86%) white needles of mp 61–62 8C; GC assay: 99.7%.
IR (oil film): 1356 (s), 1268 (vs), 1195 (s), 972 (s) cmÀ1. 1H
Partition coefficients were determined by GC as follows: in a
2 ml volumetric flask the given compounds (10 mg) were
extracted in a 1.00–1.00 ml mixture of pre-equilibrated
perfluoro(methylcyclohexane) and toluene. The closed vessel
was first immersed in a water bath (50 8C) for 30 min with
frequent shaking, then allowed to cool to 25 8C. After standing
overnight or longer at this temperature 300 Æ 3 ml aliquots of
the separated upper and lower phases were withdrawn and
diluted with 300 Æ 3 ml benzotrifluoride, which served as an
internal standard during GC analysis.
3
NMR (CDCl3): d = 7.56 (2H, d, JHH = 8.5 Hz, Har-2, Har-6),
3
7.13 (2H, d, JHH = 8.5 Hz, Har-3, Har-5), 3.98 (4H, s,
CH2CH2), 2.22 (3H, s, CH3). 13C NMR (CDCl3): d = 145.6
(1C, s, Car-1), 132.7 (1C, s, Car-4), 130.3 (2C, s, Car-2, Car-5),
1
128.3 (2C, s, Car-3, Car-3), 120.5 (3C, q, JCF = 293 Hz,
(CF3)3C), 79.8 (1C, m, 2JCF = 29 Hz, (CF3)3C), 67.7 (1C, s, C–
O–CH2), 67.4 (1C, s, CH2–OTs), 21.9 (1C, s, CH3). 19F NMR
(CDCl3): d = À71.0 (9F, s, 3CF3). Anal. Calcd for
C13H11F9O4S (434.28): C, 36.0; H, 2.6; F, 39.4; S, 7.4. Found:
C, 35.7; H, 2.8; F, 39.6; S, 7.2.
The molar volumes of amines listed in Table 2 were
estimated using the following group increments (zV/
cm3 molÀ1): CF3 54.8; CF2 23.1; CH3 33.5; CH2 16.1, C
À19.2; O 3.8; NH2 19.2; NH 4.6; and N À9.4. Thus,
VIÀc = 6 Â VCF + 4 Â VCH + 2 Â VO + 2 Â VC + 1 Â VNH
=
3
2
6 Â 54.8 + 4 Â 16.1 + 2 Â 3.8 + 2 Â (À19.2) + 1 Â 4.6 = 367
cm3 molÀ1
4.5. 2-{2-[1,1-Bis(trifluoromethyl)-2.2.2-trifluoroethoxy]-
ethyl}-isoindole-1,3-dione (5)
.
4.2. Sodium nonaflouoro-tert-butoxide (2)
4.5.1. Method A: Mitsunobu alkylation
To a stirred solution of N-2-hydroxyethyl-phthalimide, 6
(1.91 g, 10 mmol) and Ph3P (3.15 g, 12 mmol) in ether (50 ml)
a solution of diisopropyl azodicarboxylate (2.42 g, 12 mmol) in
ether (8 ml) was added at 5 8C for 5 min. Then a solution of
perfluoro-tert-butanol (2.36 g, 10 mmol) in ether (10 ml)
(caution: toxic!) was added to the mixture and stirred overnight
at r.t. The cubic crystals of the Ph3PO*diisopropyl hydrazo-
dicarboxylate complex were collected by filtration and washed
with ether (20 ml) and dried over P2O5 in vacuum to afford
3.51 g (74%) side product. Then all the glassware were washed
together by acetone and evaporated to yield 6.0 g pale yellow
oil. Crystallized from methanol (3 ml/g) at À15 8C to afford
2.90 g (71%) white flakes with mp 66–70 8C; reported [12] mp
75–76 8C; GC assay: 99%.
Perfluoro-tert-butyl alcohol, 1 (236 g, 1.00 mol) (caution:
toxic!) was added to a stirred solution of NaOH (40 g, 1.0 mol)
in water (200 ml) at 0 8C for 3 h, then the mixture stirred
30 min at r.t. The clear solution was evaporated in vacuum
(Rotavap, 16 mmHg) and the residue obtained was dried in a
vacuum desiccator over P2O5 to give 2 as white crystalline
product (258 g, 1.00 mol, 100%).
Mp 143 8C, lit. [17] mp 143 8C. IR (powder film): 1237 (vs),
1200 (vs), 1173 (s), 968 (vs) cmÀ1
.
4.3. 2-[1,1-Bis(trifluoromethyl)-2.2.2-trifluoroethoxy]-
ethyl alcohol (3)
A mixture of sodium perfluoro-tert-butoxide, 2 (5.0 g,
19.4 mmol) and 2-bromoethanol (2.42 g, 19.4 mmol) in DMF
(15 ml) was stirred and heated in an ꢀ110 8C oil bath for 2 h.
Then the mixture was diluted with water (75 ml), cooled to r.t.
and the heavier product phase was separated. It was washed
with water (3Â 1 ml), dried (Na2SO4) and distilled at ambient
pressure to afford 4.12 g (76%) colorless oil of bp 124 8C; lit.
[6f] bp 125 8C/740 mmHg; GC assay: 97.0%.
4.5.2. Method B: N-alkylation of potassium phthalimide
A mixture of nonafluoro-tert-butyloxyethyl-tosylate, 4
(17.4 g, 40 mmol) and potassium phthalimide (14.8 g, 80 mmol)
in DMF was stirred and heated at 110 8C for 2 h. Then it was
diluted with water (300 ml) and extracted with CH2Cl2 (3Â
40 ml). The CH2Cl2 layer consecutively was washed with 1 M
NaOH (20 ml), water (2Â 20 ml), dried (MgSO4), filtered and

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
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evaporated. Yield: 10.7 g (65%) white crystals, mp 75–76 8C/
CH2Cl2; GC assay: 99%.
23 mmol) and liquid methyl amine (bp = À6 8C, 40 ml),
flushed with N2 and sealed at À78 8C. Then the mixture was
allowed to warm up and stirred at r.t. for 17 h (caution: safety
shield!). After opening the ampoule the methyl amine was
evaporated and the residue made alkaline by the addition of 2N
K2CO3 (50 ml) and steam-distilled. The separated lower phase
(5.9 g) was dried (Na2SO4) and short path distilled at ambient
pressure. The main fraction was collected at 140–160 8C bath
temperature. Yield 4.62 g, (69%) colorless oil; GC assay:
99.0%.
IR (oil film): 2983 (w), 1714 (vs), 1311 (s), 1251 (vs), 1160
(s), 969 (s), 717 (s) cmÀ1. 1H NMR (CDCl3): d = 7.85 (2H, m,
Har-3, Har-6), 7.73 (2H, m, Har-4, Har-5), 4.25 (2H, t,
3
3JHH = 5.1 Hz, OCH2), 3.99 (2H, t, JHH = 5.1 Hz, CH2N).
13C NMR (CDCl3): d = 168.2 (2C, s, C O), 134.5 (2C, s, Car-1,
Car-2), 132.2 (2C, s, Car-3, Car-6), 123.8 (2C, s, Car-4, Car-5),
1
120.4 (3C, q, JCF = 293 Hz, (CF3)3C), 80.0 (1C, m,
2JCF = 29 Hz, (CF3)3C), 66.8 (1C, s, OCH2), 37.7 (1C, s,
CH2N). 19F NMR (CDCl3): d = À71.1 (9F, s, 3CF3). Anal.
Calcd for C14H8F9NO3 (409.21): C, 41.1; H, 2.0; F, 41.8; N, 3.4.
Found: C, 40.8; H, 2.2; F, 41.6; N, 3.6.
IR (oil film): 3357 (w), 2978 (w), 1167 (vs), 1160 (vs), 972
1
3
(vs) cmÀ1. H NMR (CDCl3): d = 4.12 (2H, t, JHH = 5.1 Hz,
OCH2), 2.84 (2H, t, 3JHH = 5.1 Hz, CH2N), 2.44 (3H, s, CH3),
1.97 (1H, broad, NH). 13C NMR (CDCl3): d = 120.5 (3C, q,
1JCF = 293 Hz, (CF3)3C), 79.8 (1C, m, 2JCF = 29 Hz, (CF3)3C),
4.6. 2-[1,1-Bis(trifluoromethyl)-2.2.2-trifluoroethoxy]ethyl
amine (I-a)
69.3 (1C, s, OCH2), 50.9 (1C, s, CH2N), 36.0 (1C, s, CH3). 19
F
NMR (CDCl3): d = À71.1 (9F, s, 3CF3). Anal. Calcd for
C7H8F9NO (293.13): C, 28.7; H, 2.8; F, 58.3; N, 4.8. Found: C,
28.4; H, 2.9; F, 58.0; N, 4.6.
4.6.1. Method A: hydrazinolysis of N-alkylphthalimides
To a solution of phthalimide, 5 (10.7 g, 26 mmol) in
methanol (35 ml) hydrazine hydrate (1.4 ml, 29 mmol) was
added and refluxed for 1 h. After the addition of 12 M HCl
(30 ml) and 3 h boiling the mixture was evaporated (Rotavap)
in vacuum. The solid residue was made alkaline by 10N KOH
(10 ml) and steam-distilled. Then the lower product layer was
carefully separated from water phase (difficult to recognize
phase boundary by naked eyes), dried (MgSO4) and purified by
short path distillation at ambient pressure. Yield: 3.83 g (53%)
colorless oil of bp 110 8C; GC assay: 99.7%.
4.8. N,N-Bis{2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]-ethyl} methanesulfonamide (7)
A mixture of N,N-bis(2-mesyloxyethyl)mesylamide [13]
(5.0 g, 14.7 mmol; caution: toxic! [14]), sodium perfluoro-tert-
butoxide, 2 (8.4 g, 33 mmol) and DMF (50 ml) was stirred
under an N2 atmosphere at 100 8C for 5 h. Then most of the
solvent was removed by distillation (Rotavap, 16 mmHg) and
the residue was partitioned between water (25 ml) and ether
(3Â 10 ml). The ether layer was separated and washed with
water (3Â 10 ml), then dried (Na2SO4). After removal of ether
the residue was fractionated in vacuum to afford 6.40 g (70%)
colorless distillate of bp 130–132 8C/0.5 mmHg, which
solidified at r.t., mp 41–42 8C; GC assay: 96.5%.
4.6.2. Method B: ammonolysis of tosylate
A stainless steel autoclave supplied with a magnetic stirrer
bar was charged with diglyme (10 ml) and perfluoro-tert-
butyloxyethyl tosylate, 4 (10 g, 23 mmol) and then cooling by
an acetone-dry ice mixture, liquid ammonia (40 ml) was
condensed to it. After closing the autoclave, the mixture was
stirred at 40 8C for 24 h (13 bar). Then it was cooled back,
opened and the mixture was transferred to a pre-cooled
distillation apparatus and the ammonia was evaporated (bp
À33 8C). The residue was mixed with 4 M NaOH (100 ml) and
steam-distilled. The lower phase was separated, dried (Na2SO4)
and distilled at ambient pressure using a short path apparatus.
The main fraction was collected at 140 8C bath temperature to
afford 3.04 g (47%) colorless oil; GC assay: 99.7%.
IR (powder film): 3015 (w), 2986 (w), 2943 (w), 1338 (s),
1
1310 (s), 1261 (vs), 1149 (s), 972 (s), 727 (s) cmÀ1. H NMR
(CDCl3): d = 4.26 (4H, t, 3JHH = 5.2 Hz, 2Â OCH2), 3.64 (4H,
3
t, JHH = 5.2 Hz, 2Â CH2N), 2.92 (3H, s, CH3). 13C NMR
1
(CDCl3): d = 120.1 (6C, q, JCF = 292 Hz, 2Â (CF3)3C), 78.5
2
(2C, m, JCF = 29 Hz, 2Â (CF3)3C), 68.9 (2C, s, 2Â OCH2),
47.9 (2C, s, CH2NCH2), 38.8 (1C, s, CH3). 19F NMR (CDCl3):
d = À71.1 (18F, s, 6CF3). Anal. Calcd for C13H11F18NO4S
(619.27): C, 25.2; H, 1.8; F, 55.2; N, 2.3; S, 5.2. Found: C, 25.0;
H, 2.0; F, 54.9; N, 2.1; S, 4.9.
IR (oil film): 3386 (w), 2972 (w), 1256 (vs), 1159 (s), 972
3
1
(s) cmÀ1. H NMR (CDCl3): d = 4.05 (2H, t, JHH = 4.8 Hz,
3
OCH2), 2.97 (2H, t, JHH = 4.8 Hz, CH2N), 1.52 (2H, broad,
4.9. Bis{2-[1,1-bis(trifluoromethyl)-2.2.2-trifluoroethoxy]-
ethyl} amine (I-c)
1
NH2). 13C NMR (CDCl3): d = 120.5 (3C, q, JCF = 293 Hz,
2
(CF3)3C), 79.8 (1C, m, JCF = 29 Hz, (CF3)3C), 72.3 (1C, s,
OCH2), 41.9 (1C, s, CH2N). 19F NMR (CDCl3): d = À70.9 (9F,
s, 3CF3). Anal. Calcd for C6H6F9NO (279.11): C, 25.8; H, 2.2;
F, 61.3; N, 5.0. Found: C, 25.5; H, 2.4; F, 61.0; N, 5.1.
The protected amine, 7 (3 g, 4.8 mmol) and 96% H2SO4
(8 ml) was sealed in a Pyrex ampule and heated at 100 8C for
30 h (caution: safety shield!). Then the warm (60 8C) mixture
was poured to cold water (50 ml) and the precipitated crystals
were filtered and washed with water to afford 2.43 g white solid
of mp 165–176 8C. It was found to be a mixture of sulfate
(B2 Â H2SO4, calcd S 2.8%) and hydrosulfate (B Â H2SO4,
calcd S 5.1%) salts, since microanalysis showed 3.7% S
content. To isolate this amine in pure state 2.41 g of the above
4.7. Methyl 2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]ethyl amine (I-b)
A Pyrex ampoule supplied with a magnetic stirrer bar was
charged with nonafluoro-tert-butyloxyethyl tosylate, 4 (10 g,

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1502
salt-mix was partitioned between 1 M NaOH (10 ml) and ether
(2Â 10 ml), then the separated ether phases were combined,
dried (Na2SO4) and distilled at 20 mmHg using 120 8C bath
during the collection of the main fraction. Yield: 1.78 g (70% to
MesNR2) colorless oil; GC assay: 99.9%.
4.12. 1-[1,1-Bis(trifluoromethyl)-2.2.2-trifluoroethoxy]-
ethylamino-4.4.5.5.6.6.7.7.8.8.9.910.10.11.11.11-
heptadecafluoroundecane hydrochloride (I-d*HCl)
Prepared by the reaction of the amine I-d (0.30 g) in ether
(1.0 ml) with three drops of (CH3)3SiCl and CH3OH. The
precipitate formed was filtered, washed with ether and dried
to yield 0.26 g white crystals of mp 151–153 8C.
IR (oil film): 2974 (w), 2917 (w), 1253 (vs), 1162 (s), 972
3
1
(s) cmÀ1. H NMR (CDCl3): d = 4.16 (4H, t, JHH = 4.8 Hz,
3
2Â OCH2), 2.95 (4H, t, JHH = 4.8 Hz, CH2NHCH2). 13C
1
NMR (CDCl3): d = 120.5 (6C, q, JCF = 292 Hz, 2Â
IR (KBr): 2972 (w), 2728 (w), 1312 (s), 1360 (vs), 1151 (s),
973(s) cmÀ1. 1H NMR(CD3OD): d = 4.45(2H, t, 3JHH = 5.0 Hz,
2
(CF3)3C), 79.9 (2C, m, JCF = 29 Hz, 2Â (CF3)3C), 69.6
(2C, s, 2Â OCH2), 48.6 (2C, s, CH2NHCH2). 19F NMR
(CDCl3): d = À71.1 (18F, s, 6CF3). Anal. Calcd for
C12H9F18NO2 (541.18): C, 26.6; H, 1.7; F, 63.2; N, 2.6.
Found: C, 26.3; H, 2.0; F, 62.9; N, 2.8.
3
OCH2), 3.49 (2H, t, JHH = 5.0 Hz, OCH2CH2N), 3.25 (2H, t,
3
3JHH = 8.0 Hz, NCH2CH2CH2), 2.40 (2H, tt, JHH = 8.0 Hz,
3JHF = 18 Hz, CH2CF2), 2.11(2H, t, 3JHH = 8.0 Hz,
NCH2CH2CH2). 13C NMR (CD3OD): d = 120.5 (3C, q,
1JCF = 292 Hz, (CF3)3C), 110–118 (Rf8 overlapping multiplets),
79.9 (1C, m, 2JCF = 29 Hz, (CF3)3C), 67.7 (1C, s, OCH2), 48.7
(1C, s, OCH2CH2), 48.3 (1C, s, NCH2), 29.2(1C, t, 2JCF = 22 Hz,
CH2CF2), 18.8 (1C, s, NCH2CH2CH2). 19F NMR (CD3OD):
4.10. Bis{2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]-ethyl} amine hydrochloride (I-c*HCl)
3
Prepared by the reaction of the amine (0.30 g) in ether
(1.0 ml) with three drops of (CH3)3SiCl and CH3OH. The
precipitate formed was filtered, washed with ether and dried to
yield 0.28 g white crystals, mp 145–180 8C (decomp).
d = À71.9 (9F, s, (CF3)3C), À82.9 (3F, t, JCF = 9.7 Hz, CF3),
À115.8 (2F, broad m), À123.4 (6F, broad m), À124.3 (2F, broad
m), À124.9 (2F, broad m), À127.8 (2F, broad m).
IR (KBr): 2971 (w), 1311 (s), 1264 (vs), 1159 (s), 972 (s),
727 (m) cmÀ1. 1H NMR (CD3OD): d = 4.85 (2H, broad, NH2),
4.13. Dimethyl 2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]-ethyl amine (I-e)
3
4.55 (4H, t, JHH = 5.1 Hz, 2Â OCH2), 3.56 (4H, t,
3JHH = 5.1 Hz, CH2NHCH2). 13C NMR (CD3OD): d = 120.5
(6C, q, 1JCF = 292 Hz, 2Â (CF3)3C), 79.8 (2C, m, 2JCF = 30 Hz,
2Â (CF3)3C), 66.0 (2H, s, 2Â OCH2), 47.4 (2C, s,
CH2NHCH2). 19F NMR (CD3OD): d = À72.0 (18F, s, 6CF3).
4.13.1. Method A: aminolysis of the tosylate
In a Pyrex ampoule dimethyl amine (5 ml, ꢀ80 mmol) was
condensed to (nonafluoro-tert-butyloxy)ethyl-tosylate,
4
(2.0 g, 4.6 mmol) and it was sealed under N2 and the mixture
was kept at 25 8C for 20 h (caution: safety shield!). Unreacted 4
could not be detected by GC at this point. About 2N K2CO3
(20 ml) was added to the reaction mixture and it was then
steam-distilled. The separated lower phase was dried (Na2SO4)
and distilled to afford 0.75 g (53%) colorless liquid, bp 116 8C;
GC assay: 98.0%.
4.11. 1-[1,1-Bis(trifluoromethyl)-2.2.2-trifluoroethoxy]-
ethylamino-4.4.5.5.6.6.7.7.8.8.9.910.10.11.11.11-
heptadecafluoroundecane (I-d)
A Pyrex ampoule was charged with nonafluoro-tert-
butyloxyethyl tosylate, 4 (4.34 g, 10 mmol) and 3-perflluor-
ooctyl-1-propylamine (9.54 g, 20 mmol), then sealed under an
N2 atmosphere. Then the mixture was heated at 100 8C for 16 h
(caution: safety shield!) and carefully opened at r.t. The crude
product was partitioned between ether (100 ml) and 2N K2CO3
(100 ml). The separated organic phase was dried (Na2SO4),
then fractionated by vacuum distillation to afford 4.45 g (60%
to ROTs) colorless liquid with bp 150–155 8C/16 mmHg; GC
assay: 97.5%.
4.13.2. Method B: Williamson-synthesis
A solution of freshly liberated and distilled 2-dimethyla-
minoethyl chloride (1.08 g, 10 mmol) (caution: toxic [14],
safety shield!) and that of sodium perfluoro-tert-butoxide, 2
(2.84 g, 11 mmol) in diglyme (20 ml) was sealed in an ampoule
of 200 ml volume under N2 and the mixture stirred at 100 8C
for 24 h. Then the mixture was diluted with water (50 ml) and
the separated lower phase was washed with water (2Â 25 ml),
dried (Na2SO4) and distilled at ambient pressure to afford
1.11 g (36%) colorless liquid, bp 116–117 8C; GC assay:
98.4%.
IR (oil film): 2960 (w), 1253 (vs), 1154 (s), 973 (s) cmÀ1
.
3
1H NMR (CDCl3): d = 4.14 (2H, t, JHH = 5.0 Hz, OCH2),
3
2.92 (2H, t, JHH = 5.0 Hz, OCH2CH2N), 2.75 (2H, t,
3
3JHH = 8.0 Hz, NCH2CH2CH2), 2.18 (2H, tt, JHH = 8.0 Hz,
3
3JHF = 18 Hz, CH2CF2), 1.79 (2H, t, JHH = 8.0 Hz,
IR (oil film): 2980 (w), 2830 (w), 1254 (vs), 1158 (s), 972
1
NCH2CH2CH2). 13C NMR (CDCl3): d = 120.5 (3C, q,
(s) cmÀ1. H NMR (CDCl3): d = 4.12 (2H, t, JHH = 5.1 Hz,
3
2
3
OCH2), 2.64 (2H, t, JHH = 5.1 Hz, OCH2CH2N), 2.29 (6H, s,
1JCF = 292 Hz, (CF3)3C), 79.9 (1C, m, JCF = 21 Hz,
(CF3)3C), 69.7 (1C, s, OCH2), 48.7 (1C, s, OCH2CH2),
2Â CH3). 13C NMR (CDCl3): d = 120.5 (3C, q, 1JCF = 293 Hz,
2
2
48.4 (1C, s, NCH2CH2CH2), 28.8 (1C, t, JCF = 22 Hz,
(CF3)3C), 79.8 (1C, m, JCF = 29 Hz, (CF3)3C), 68.5 (1C, s,
CH2CF2), 20.9 (1C, s, NCH2CH2CH2). 19F NMR (CDCl3):
d = À71.0 (12F, s, 4CF3). Anal. Calcd for C17H11F26NO
(739.24): C, 27.6; H, 1.5; F, 66.8; N, 1.9. Found: C, 27.2; H,
1.8; F, 66.5; N, 2.0.
OCH2), 58.5 (1C, s, CH2N), 46.0 (2C, s, CH3). 19F NMR
(CDCl3): d = À71.1 (9F, s, 3CF3). Anal. Calcd for C8H10F9NO
(307.16): C, 31.3; H, 3.3; F, 55.7; N, 4.6. Found: C, 31.1; H, 3.0;
F, 55.4; N, 4.8.

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
1503
4.14. Methyl bis{2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]-ethyl} amine (I-f)
Acknowledgment
We thank the Hungarian Scientific Research Foundation
(OTKA T 43738).
Bis(2-chloroethyl) methyl amine HCl (1.0 g, 5.2 mmol)
(caution: toxic [14], safety shield!), sodium nonafluoro-tert-
butoxide, 2 (4.15 g, 16.1 mmol) and diglyme (20 ml) was
sealed in an ampule under N2 and stirred at 100 8C for 24 h. The
mixture was steam-distilled, and separated lower phase washed
with water (3Â 10 ml) and distilled to afford 1.95 g oil at 130–
140 8C bath and 20 mmHg. The product contained some 6%
diglyme, thus it was further purified by partitioning between
methanol (5 ml) and FC-72 (3Â 5 ml). The fluorous solvent was
recovered first by distillation at ambient pressure, while the
amine obtained at 20 mmHg using an 130–140 8C oil bath. The
title amine was obtained as a colorless liquid; yield: 1.45 g
(53%); GC assay: 99.2%.
References
´ ´
[1] (a) I.T. Horvath, J. Rabai, Science 266 (1994) 72–75;
´
´
(b) I.T. Horvath, J. Rabai, US Patent 5,463,082 (Exxon Research and
Engineering Co.) October 31, 1995 (application: July 8, 1993); Chem.
Abstr. 123 (1995) 87349.
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[2] (a) I.T. Horvath, Acc. Chem. Res. 31 (1998) 641–650;
´
´
´
(b) J. Rabai, Z. Szlavik, I.T. Horvath, in: J. Clark, D. MacQuarrie (Eds.),
Handbook of Green Chemistry and Technology, Blackwell Science,
Oxford, 2002 , pp. 502–523 (Chapter 22);
(c) J.A. Gladysz, D.P. Curran (Eds.), Tetrahedron, vol. 58, 2002, pp.
3823–4131;
IR (oil film): 2966 (w), 1253 (vs), 1157 (s), 972 (s) cmÀ1. 1H
NMR (CDCl3): d = 4.13 (4H, t, 3JHH = 5.6 Hz, 2Â OCH2), 2.84
(4H, t, 3JHH = 5.6 Hz, CH2NCH2), 2.42 (3H, s, CH3). 13C NMR
(d) J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.), Handbook of Fluorous
´
Chemistry, Wiley/VCH, Weinheim, 2004;
(e) J.A. Gladysz, Angew. Chem. Int. Ed. 44 (2005) 5766–5768;
(f) M. Freemantle, Chem. Eng. News 83 (2005) 39–42.
´
[3] (a) I.T. Horvath, G. Kiss, R.A. Cook, J.E. Bond, P.A. Stevens, J.
1
(CDCl3): d = 120.4 (6C, q, JCF = 292 Hz, 2Â (CF3)3C), 79.8
2
(2C, m, JCF = 29 Hz, 2Â (CF3)3C), 68.3 (2C, s, 2Â OCH2),
´
Rabai, E.J. Mozeleski, J. Am. Chem. Soc. 120 (1998) 3133–
56.6 (2C, s, CH2NCH2), 43.1 (1C, s, CH3). 19F NMR (CDCl3):
d = À71.2 (18F, s, 6CF3). Anal. Calcd for C13H11F18NO2
(555.21): C, 28.1; H, 2.0; F, 61.6; N, 2.5. Found: C, 27.8; H, 2.2;
F, 61.3; N, 2.7.
3143;
´
(b) J.A. Gladysz, in: J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.),
Handbook of Fluorous Chemistry, Wiley/VCH, Weinheim, 2004
pp. 41–55 (Chapter 5).
,
´
[4] (a) J.A. Gladysz, in: J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.),
Handbook of Fluorous Chemistry, Wiley/VCH, Weinheim, 2004 , pp.
24–40 (Chapter 4);
4.15. Tris{2-[1,1-bis(trifluoromethyl)-2.2.2-
trifluoroethoxy]-ethyl}amine (I-g)
´
(b) J.A. Gladysz, C. Emnet, J. Rabai, in: J.A. Gladysz, D.P. Curran, I.T.
´
Horvath (Eds.), Handbook of Fluorous Chemistry, Wiley/VCH, Wein-
heim, 2004 , pp. 56–100 (Chapter 6);
´
(c) D.P. Curran, in: J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.),
Tris(2-chloroethyl)amine HCl (1.0 g, 4.1 mmol) (caution:
toxic[14], safety shield!), sodium perfluoro-tert-butoxide, 2
(4.3 g, 17 mmol) and diglyme (20 ml) were sealed in an
ampoule under N2 and stirred at 100 8C for 24 h. The mixture
was steam-distilled and the lower phase separated at 0 8C, then
dissolved in methanol (5 ml) and extracted with FC-72 (3Â
5 ml). The FC solvent was recovered by distillation at ambient
pressure, while the residue fractionated in vacuum to afford
1.10 g (33%) colorless oil, bp 140 8C/20 mmHg; GC assay:
93.4%. This crude product was converted to R3N Â HCl by
treating it in a small volume of methanol with an excess of
(CH3)3SiCl. The precipitated salt was recrystallized from
boiling methanol (20 ml/g) to afford white crystals of mp 110–
130 8C (decomp). The purified amine was isolated by treating
the HCl salt with an excess of 1N NaOH and consecutive
extraction with ether. Then the separated organic phase was
dried (Na2SO4) and the solvent evaporated in vacuum (Rotavap,
20 mmHg). The recovery of the title amine was 60%; GC assay:
99.0%.
Handbook of Fluorous Chemistry, Wiley/VCH, Weinheim, 2004 , pp.
101–127 (Chapter 7);
´
(d) D.P. Curran, in: J.A. Gladysz, D.P. Curran, I.T. Horvath (Eds.),
Handbook of Fluorous Chemistry, Wiley/VCH, Weinheim, 2004 , pp.
128–156 (Chapter 8).
[5] C.S. Wilcox, V. Gudipati, H. Lu, S. Turkyilmaz, D.P. Curran, Angew.
Chem. Int. Ed. 44 (2005) 6938–6940.
[6] For syntheses of (CF3)3COH, see:
(a) I.L. Knunyants, B.L. Dyatkin, A. Izv, Nauk SSSR, Ser. Khim. 5 (1964)
923–925;
(b) R. Filler, R.M. Schure, J. Org. Chem. 32 (1967) 1217–1219;
(c) F.J. Pavlik, P.E. Toren, J. Org. Chem. 35 (1970) 2054–2056;
(d) S.P. Kotun, J.D.O. Anderson, D.D. DesMarteau, J. Org. Chem. 57
(1992) 1124–1131;
(e) L.A. Babadzhanova, N.V. Kirij, Yu.L. Yagupolskii, W. Tyrra, D.
Naumann, Tetrahedron 61 (2005) 1813–1819;
(f) F.J. Pavlik, US Patent 3,385,904 (Minnesota Mining and Manufactur-
ing Co.) May 28, 1968 (application: October 30, 1962); Chem. Abstr. 69
(1968) 26753x;
(g) V. Weinmayr, US Patent 3,317,616 (du Pont de Nemours, E. I., and
Co.) May 2, 1967 (application: September 1, 1964); Chem. Abstr. 67
(1967) 63755d;
IR (oil film): 2973 (m), 2915 (m), 2851 (m), 1250 (vs), 1154
(vs), 735 (vs), 727 (vs) cmÀ1. 1H NMR (CDCl3): d = 4.06 (6H,
(h) A.V. Fokin, I.N. Krotovich, R.Sh. Valiev, Yu. N. Studnev, USSR SU
Patent 1,567,566 May 30, 1990 (application: August 15, 1988); Chem.
Abstr. 113 (1990) 171491s;
3
3
t, JHH = 5.4 Hz, 3Â OCH2), 2.94 (6H, t, JHH = 5.4 Hz,
N(CH2–)3). 13C NMR (CDCl3): d = 120.6 (9C, q,
(i) F.J. Pavlik, US Patent 4,010,212 (Minnesota Mining and Manufactur-
ing Co.) March 1, 1977 (application: June 14, 1976); Chem. Abstr. 86
(1977) 189226.
1JCF = 292 Hz, 3Â (CF3)3C), 79.9 (3C, m, JCF = 29 Hz, 3Â
2
(CF3)3C), 69.6 (3C, s, 3Â OCH2), 55.4 (3C, s, N(CH2–)3). 19
F
[7] (a) D.P. Graham, V. Weinmayr, J. Org. Chem. 31 (1966) 957–958;
(b) J.D.O. Anderson, D.D. DesMarteau, J. Fluorine Chem. 77 (1996)
147–152;
NMR (CDCl3): d = À71.1 (27F, s, 9CF3). Anal. Calcd for
C18H12F27NO3 (803.26): C, 26.9; H, 1.5; F, 63.9; N, 1.7. Found:
C, 26.7; H, 1.9; F, 63.6; N, 1.9.
(c) G.J. Chen, L.S. Chen, J. Fluorine Chem. 79 (1996) 125–131.

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D. Szabo et al. / Journal of Fluorine Chemistry 127 (2006) 1496–1504
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