Practice of fluorous biphase chemistry: Convenient synthesis of novel fluorophilic ethers via a Mitsunobu reaction

Article abstract of DOI:10.1016/S0022-1139(02)00027-1

The evolution of the term fluorous is addressed first, then a concise terminology is proposed, including fluorous partition coefficient, specific fluorophilicity and fluorousness. Some examples are shown for the design of higher generation fluorophilic mo

Full text of DOI:10.1016/S0022-1139(02)00027-1

Journal of Fluorine Chemistry 114 (2002) 199–207
Practice of fluorous biphase chemistry: convenient synthesis of
novel fluorophilic ethers via a Mitsunobu reaction
a,*
J o´ zsef R a´ bai , D e´ nes Szab o´ , Eszter K. Borb a´ s , Istv a´ n K o¨ vesi , Istv a´ n K o¨ vesdi ,
a
a
a
b
c
Antal Cs a´ mpai , Agnes G o¨ m o¨ ry , Valeriy E. Pashinnik , Yuriy G. Shermolovich
d
e
e
´
a
Department of Organic Chemistry, E o¨ tv o¨ s Lor a´ nd University, P.O. Box 32, H-1518, Budapest 112, Hungary
b
EGIS Pharmaceuticals Ltd., P.O. Box 100, H-1475 Budapest, Hungary
Department of General and Inorganic Chemistry, E o¨ tv o¨ s Lor a´ nd University, P.O. Box 32, H-1518, Budapest 112, Hungary
c
d
Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest, Hungary
e
Institute of Organic Chemistry, National Academy of Sciences, Murmanskaya Street 5, 02094 Kiev, Ukraine
Received 14 September 2001; accepted 31 October 2001
Dedicated to Professor Andr a´ s Messmer on the occasion of his 80th birthday.
Abstract
The evolution of the term fluorous is addressed first, then a concise terminology is proposed, including fluorous partition coefficient,
specific fluorophilicity and fluorousness. Some examples are shown for the design of higher generation fluorophilic molecules, involving
Class I to Class III ponytails. Fluorophilic ethers of the structure of ArC(CF
3
)
2
O(CH
2
)
m
(CF
2
)
in high yields, when 2-aryl-1,1,1,3,3,3-hexafluoro-propanols are reacted either with trifluoroethyl- and 1H,1H-perfluorooctyl triflates (NaH/
n
F (m ¼ 1, n ¼ 1, 7; m ¼ 3, n ¼ 8) are obtained
DMF, Williamson ether synthesis) or with 3-perfluorooctyl-propanol (Ph P/EtO CN=NCO Et/PhCF , Mitsunobu reaction), respectively.
3
2
2
3
Fluorophilic phenol- and perfluoro-tert-butyl ethers can also be prepared effectively by the latter method. In case of higher homologues
14/CH OH). Specific fluorophilicity values of target molecules are
(
n ¼ 7, 8) product isolation can be facilitated using fluorous extraction (C
6
F
3
estimated using a 2D method and compared with experimentally determined ones. # 2002 Elsevier Science B.V. All rights reserved.
Keywords: Fluorine; Specific fluorophilicity; Mitsunobu reaction; Perfluoroalkylmethyl triflates
1
. Introduction
unique physical and chemical properties associated with
perfluorinated solvents, such as hydrophobicity and lipo-
phobicity (amphiphobic [17]), inertness, non-toxicity, and
easy separation [1–16].
The fluorous phase (i.e. the C–F bond rich part of a
multiphase system [1,2]) has been involved in several inno-
vative catalyst and reagent immobilization protocols, fluor-
ous isolation techniques, and seems to alter the way of our
thinking about synthetic chemistry [1–15]. In this respect not
only chemical reactions, but product separations should also
be considered at the design level of a chemical synthesis
The concept of fluorous biphase systems noticed by Vogt
[18] in 1991, but first drafted by Horv a´ th and R a´ bai [1] in
1994, served as a basis of several novel applications in
homogeneous catalytic chemistry utilizing the temperature
dependent miscibility of perfluorocarbon fluids with stan-
dard organic solvents [1,3,5,7,18]. Soon afterwards, Curran
and coworkers introduced a series of synthetic and purifica-
tion methods, called fluorous synthesis, in which organic
target molecules are rendered selectively soluble in the
fluorous phase by the temporary or permanent attachment
of adequate fluorous labels [10–13]. Fluorous mixture synth-
esis, developed by Curran and coworkers [14] is the most
recent application of the power of fluorous-tagging coupled
[
1,3,7,12]. The native phasephilicity (e.g. hydrophilic, lipo-
philic, fluorophilic, etc.) of the components of a chemical
reaction will determine their separation [16]. Thus, fluorous
extraction can effectively be used for fluorophilic com-
pounds [3,7,16], while chromatography over F-SiO2 is
the method of choice for the sequential isolation of untagged
and F-tagged (i.e. perfluoroalkylated) molecules [13]. The
popularity of these fluorous techniques is partly due to the
with F-SiO chromatography [13] to allow separation of a
2
*
mixture of related compounds by their ‘fluorine content’ (or
‘fluorousness’ [16,19]).
Corresponding author. Tel.: þ36-1-209-0602; fax: þ36-1-209-0602.
E-mail address: rabai@szerves.chem.elte.hu (J. R a´ bai).
0022-1139/02/$ – see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 0 2 7 - 1

200
J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
1.2. First and higher generation fluorophilic compounds
Scheme 1. Structural pattern of a ‘classic’ fluorophile.
The question ‘what makes a compound particularly solu-
ble in the fluorous phase?’ is still unanswered. However, the
most important fact is that molecules rendered soluble in the
fluorous phase usually do not have exposed functional
groups capable for attractive intermolecular interactions
via directional forces (e.g. dipole–dipole, hydrogen-bonding,
p–p interaction, etc.); only weak interactions via universal
attractive forces are appearing [24].
1
.1. Terminology
The key issues of synthesis design besides choosing
appropriate chemical reactions are solvent selection and
the purposeful tuning of the phasephilicities of the involved
molecules [1,3,5,7,12,16,20]. The term of phasephilicity
[
nophilic, hydrophilic, fluorophilic, and scCO -philic [21]
16] could be classified such as (1) monophilic: e.g. orga-
A very simple method for the estimation of fluorophili-
cities using only 2D structural formulae of compounds is
based on the following experimental observation: the lower
the calculated Hildebrand parameter, the higher the specific
fluorophilicity of the molecule [16].
A ‘universal protocol’ for designing fluorophilic mole-
cules consists of assembling several structural fragments to a
molecule in a way that allows the required chemistry, while
keeping the calculated Hildebrand parameter (dcalcd) of the
final constitution at the lowest value possible.
2
(
only one type of phase character is expressed in the
molecules); (2) amphiphilic (two different types of domains
are involved) [22]; or (3) multiphilic (more than two types of
domains are involved in the complex structures) [23]. In
certain cases, supercritical carbon dioxide (scCO ) can be a
2
substitute for fluorocarbon solvents [15,21].
A fluorous molecule, can be regarded as the union of
fluorous (perfluorocarbon-like, rich in C–F bonds) and
nonfluorous structural fragments and has a constitution as
shown in Scheme 1.
Simple calculations suggest (Eq. (3), that this can be
achieved by incorporating CF groups and branching in
3
If the above entity (Scheme 1) has a fluorous partition
coefficient [20] value larger than one, PFBS > 1, or fluor-
the fluorous ponytails, along with the use of other building
blocks with low cohesive increments, such as Si(CH ) or
3
3
ophilicity value larger than zero, f ¼ lnP
> 0, [perfluor-
C(CH ) , if non-fluorous groups are considered [25].
3 3
FBS
o(methylcyclohexane)-toluene solvent pair, T ¼ 25 8C],
then it is called fluorophilic (or fluorophile) [16]. The
synthesis of a fluorophile can be easily achieved by append-
ing fluorous ponytails of appropriate number, length and
shape (topology) as demonstrated by the early examples of
the FBS concept [1–3]. At that time the word ‘fluorous’ was
reserved for the identification of the C–F bond rich part of a
multiphase system, which consisted of perfluorinated and
other solvents, fluorous ligands, catalysts, and reagents.
However, the meaning of the word fluorous expanded con-
tinuously and much of its original meaning has been lost if
phase preference was considered. Thus, compounds having
These values (dcalcd) can be estimated by a group
contribution method using Eq. (3) [25], assuming that a
compound’s phase behavior is a result of the sum of the
independent interactions of their constituents with like and
unlike molecules [24].
ꢀ
P
ꢁ
z
1=2
DU
DV
dcalcd
¼
P
(3)
z
Thus, for example isomeric ethers, such as C H CH O–
6
5
2
C(CF ) and C H C(CF ) O–CH CF , should have equal
2
3
3
6
5
3 2
3
dcalcd values and consequently similar fluorophilicities.
Furthermore, the effect of the highly electronegative
perfluoroalkyl-groups on reaction centers can be insulated
by the insertion of appropriate spacer groups in-between the
at least one perfluoroalkyl-group (R ) are called as ‘light’
fn
(
organophilic, f ¼ lnPFBS < 0) or ‘heavy’ fluorous (fluor-
ophilic, f ¼ lnPFBS > 0) ones [16]. By now, both ‘fluoro-
philicity’ and ‘fluorous phase affinity’ are the used measures
for phase preference, related to fluorous partition coefficient
R
Presently, the –(CH ) – and –Si(CH ) CH CH – groups are
fn groups and the organic domains (Scheme 1) [1,26,27].
2
n
3 2
2
2
the most preferred ones [28,29]. Since, the physical proper-
ties of hetero atoms connected to F-alkyl groups are rather
different from those of connected to alkyl groups, we
propose that these atoms be regarded as part of the fluorous
(
PFBS) [16,20]. Recently, specific fluorophilicity has been
defined for compound ‘i’, as the product of fluorophilicity
and of the ratio of the van der Waals volumes of the expelled
fluorous solvent and the entering solute molecules (Eq. (1),
ponytails (e.g. OCF , SCF , Table 1).
3 3
[
16]).
With the exception of some perfluoropolyether type sub-
stitutions [15,18,30], all relevant publications seem to rely
on the use of Class I ponytails, mostly involving n-perfluor-
oalkyl groups. The effect of branching [31] of the ponytail
on fluorous phase affinity has been addressed very recently
by both theory [16] and experiment [32].
We propose that compounds with higher generation fluor-
ous ponytails, i.e. others than listed in Class I of Table 1, be
studied for both their phase behavior and effective syntheses
VvdwðCF C F Þ
3
6 11
fspecðiÞ ¼
(1)
V
ðiÞ
vdw
While phase preferences can be easily predicted by Eq. (2),
using calculated Hildebrand parameters (dcalcd) [16], little is
known about absolute solubilities in fluorous solvents.
fspecðiÞ ¼ a À bdcalcdðiÞ ða; b are constants and a; b > 0Þ
(2)
(cf. Rule 5. ‘The structure of the fluorous ponytail’ of [16]).

J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
201
Table 1
Classification of selected fluorous ponytails
Entry
Group
Formula
M
w
F (%) Used in
FBC
a
Class I
1
2
3
4
5
6
7
CF
(CF
C(CF
3
CF
3
69
219
219
319
419
519
127
82.6
78.1
78.1
77.4
77.1
76.9
74.8
No
2
)
3
CF
3
C
C
C
C
C
4
4
6
8
F
F
F
F
9
Yes
No
3
)
3
9
(CF
(CF
(CF
2
2
2
)
5
7
9
CF
3
3
3
13
17
Yes
Yes
Yes
No
3
Scheme 2. Constitution of a lipophilic ‘CF -rich’ anion.
)
)
CF
CF
10 21
F
SF
5
SF
5
nized as a superdense fluorophilic group [16], we preferred
structures in which a number of CF groups are incor-
a
Class Ii
3
8
–12 (CF
2
)
n
X, X ¼ Cl,
, H
No
porated. Although compounds with ‘CF -rich’ functional
3
Br, I, SF
OCF
SCF
N(CF
P(CF
5
groups, such as PhC(CF3)3 [33], CH OC(CF ) [34],
3
3 3
13
14
15
16
17
18
19
3
CF
CF
3
S
85
101
152
169
67.1
56.4
75.0
67.5
No
No
No
No
No
No
Yes
HetOC(CF ) CF CF OCF(CF ) [35], PhSC(CF3)3 [36],
3 2
3
2
2
2
3
3
O
PhSeC(CF ) [37], PhN(CF ) [38,39] and HN(C(CF ) )
3 3 2
3
)
2
C
C
2
F
F
6
N
3 3
3 2
3
)
2
2
2
2
6
P
[40] are already known in the literature [41], none of these
F-groups have been involved in fluorous studies.
However, highly lipophilic tetraarylborate ions substi-
CF
CF
2
CF
CF
ORfn
2
N(Rfn)
2
C(O)CF(CF
3
)[OCF
2
-
tuted with many CF groups, which are capable of incorpor-
3
CF(CF )] OCF
3
a
m
2
2 3
CF CF
ating various cations into hydrophobic solution phases in
the form of ion pairs, have been prepared by Ichikawa and
coworkers (Scheme 2) [42].
Class III
20
C(CF
3
)
2
OCH CF
2
3
C
5
H
2
F
9
O 249
68.7
No
a
Class I–III groups contain one, two or three more atom type(s) than
fluorine, respectively.
Inspired by this work, we decided to develop effective
methods for the synthesis of novel fluorophilic compounds,
including ArC(CF ) OR , ArOCH CH CH R
and
(CF ) CO(CH ) R type ethers. Their potential for fluorous
3
2
(f)
2
2
2 fn
2
. Results and discussion
3
3
2 m fn
applications can be judged using predicted fluorophilicity
values (Table 2). It is clearly seen, that both polarity (dcalcd
In this study we aimed at identifying novel and effective
fluorous solubilizing groups, which can be made from easily
)
and volume (V ) affect phase preference. Thus, an unknown
compound like phosphine 16 with six ponytails and a large
m
accessible precursors. Since the CF group has been recog-
3
Table 2
Selected properties of partially fluorinated compounds
a
b
c
d
pred
e
exp
Entry
Compound (M
w
)
F (%)
V
m, calcd
d
calcd
f
spec, pred
f
f
f
f
1
2
3
4
5
6
7
8
9
CF
CF
3
SO
SO
2
OCH
OCH
2
CF
3
, (232.1)
49.1
64.3
43.4
44.2
52.4
63.7
63.3
63.3
62.0
52.0
58.5
65.7
60.0
61.1
71.0
65.2
159
297
191
205
245
383
422
422
438
319
399
785
798
381
424
2104
14.3
14.0
16.7
15.6
14.9
14.5
14.6
14.4
14.7
14.6
13.9
14.1
14.8
15.3
12.5
14.1
1.28
1.48
1.04
2.24
À0.32
0.92
1.10
2.25
2.33
2.60
2.26
1.76
3.16
5.64
3.83
1.19
5.39
15.1
3
2
2
R
f7, (532.1)
C
C
C
C
C
C
C
6
H
6
H
6
H
6
H
6
H
6
H
6
H
5
5
5
5
5
5
5
C(CF
C(CF
C(CF
C(CF
C(CF
C(CF
C(CF
3
)
3
)
3
)
3
)
3
)
3
)
3
)
2
2
2
2
2
2
2
Cl, (262.6)
À0.33
0.41
0.88
1.15
1.08
1.21
1.01
1.08
1.55
1.41
0.94
0.61
2.49
1.41
À2.04
À1.83
À0.62
1.90
1.46
1.39
1.16
À0.89
1.19
4.67
3.91
0.15
4.04
–
OCH
OCH
OCH
3
2
2
, (258.2)
CF , (326.2)
f7, (626.2)
3
R
O(CH f8, (690.2)
OCH(CH )Rf8, (690.2)
2 3
O(CH ) Rf8, (704.2)
2
)
2
R
3
1
1
1
1
1
1
1
0
1
2
3
4
5
6
1,3-C
1,3-C
1,3-C
6
H
6
H
6
H
4
4
4
6
[C(CF
[C(CF
[C(CF
3
3
3
)
)
)
2
2
2
OCH
OCH
3
]
2
, (438.2)
CF , (574.2)
, (1330.4)
2
3 2
]
O(CH
O(CH
f8, (622.2)
f8, (696.2)
O(CH
2
)
3
R
f8
]
2
1,3,5-IC
1,3-CF
(CF CO(CH
P{C [C(CF
H
3
[C(CF
3
)
2
2
)
3
R
f8
]
2
, (1456.3)
3
C
6
H
4
O(CH ) R
2 3
3
)
3
2 3
) R
6
H
3
3
)
2
) R ] } , (4019.2)
2 3 f8 2 3
a
b
c
d
e
f
3
(cm mol ).
À1
Calculated from group increments, see: Eq. (3), V
m
1/2
Calculated from group increments, see: Eq. (3); d (MPa ).
Estimated by regression equation fspec ¼ 10:86À0:67d, obtained for compounds 1–59 [16].
3
À1
.
f ¼ lnPFBS (i) ¼ [V
m
(i)/V
m
(CF
3
C
6
F
m 3
11)]fspec, where V (CF C
6
F
11) ¼ 196 cm mol
Determined by GC; see Section 4.
Not determined by GC; samples decomposed at injection (230 8C).

202
J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
molar volume is expected to have a fluorous partion coeffi-
6
cient, PFBSð16Þ > 10 , while its precursor arene 12 with
only two ponytails and a smaller volume, would result in
a much lower value, PFBSð12Þ ¼ 280, in spite of that
both compounds have the same calculated polarity
Scheme 3. Making arene fluorophiles with Class III ponytails.
(
dcalcd ¼ 14:1).
We noticed that the Mitsunobu reaction [48] can be applied
for the effective synthesis of ethers if 3-perfluorooctyl-
Furthermore, a knowledge of these partition values ahead
2
propanol (2eb) is used as the alcohol component (R OH),
of synthesis of target molecules could facilitate the selection
of appropriate work up procedures. Their estimation
involves the following steps:
while the yield drops significantly with 2-perfluorooctyl-
ethanol (2d) (cf. [49]), due to its facile dehydration reaction,
and finally in case of perfluoroheptyl-methanol (2cb) no
ether formation occurs (Table 3). These results can be
interpreted with the effect of the strongly electron with-
drawing perfluoroalkyl groups on reaction centers, which is
only insulated properly in the first case.
(
(
(
a) molar volume (V ) and Hildebrand parameter (dcalcd)
m
values are calculated first from group increments based
on 2D chemical structures (Eq. (3));
b) then these data are substituted for the appropriate
parameters of the regression equation (Eq. (2) to yield
specific fluorophilicity (fspec,pred) values;
However, the above reactions were performed in a solvent
BTF) providing acceptable solubility for all reaction com-
(
c) which are finally converted to fluorophilicities (Eq. (1))
and partition coefficients (f ¼ lnPFBS) according to
their definitions (Table 2).
ponents (Scheme 4). It is worth to note, that the fluorophilic
ethers formed can be separated effectively from all other
organic compounds, if the solvent is removed first by
distillation and then the residue is partitioned between a
fluorous solvent, such as FC-72 (perfluorohexanes) or per-
fluoro(methylcyclohexane) and methanol (Method B,
Table 2).
The experimental fluorophilicity values (fexp) of this set of
compounds (Entries 3–15, Table 2) determined by a simple
GC method were found to correlate well with the predic-
ted ones. However, the latter numbers are somewhat over-
estimated (R ¼ 0:94, S:D: ¼ 0:78, Fig. 1).
On the contrary, ethers with a –(CF ) COCH CF – struc-
3
2
2
2
Since 2-aryl-hexafluoro-propanols are accessible easily
with the reaction of aromatic hydrocarbons and hexafluor-
oacetone [43,44], their use for fluorous solubilisation of
aromatic reagents or catalyst precursors seems reasonable
tural fragment (3ab, 3ac and 3bb) can be obtained in
acceptable yields if trifluoroethyl- (2b) or 1H,1H-perfluor-
oheptyl triflates (2ca) are reacted with in situ formed sodium
alcoholates in DMF solution (Method A, Table 3).
(
Scheme 3).
In addition, these fluorinated ethers are expected to be
The methylation reactions took place under milder con-
ditions, where methyl methanesulfonate (2a) at room
temperature affords the appropriate ethers (3aa and 3ba)
in good yields. Unlike to Mitsunobu synthesis, the reaction
of 3-perfluorooctyl-propyl iodide (2ea) and NaOC(CF ) Ph
in DMF gave the fluorophilic ether (3ae) only in low isolated
yield, which can be ascribed to the heterogeneous nature of
this alkylation process.
very robust, such as their parent compounds, PhC(CF ) OR,
3
2
where the PhC(CF ) -fragment has been introduced as a
3
2
protecting group for alcohols using a Mitsunobu reaction
45]. Other b-CF -substituted alcohols are known as suitable
acid components, if their coupling with nonfluorinated
3
2
[
3
alcohols is considered [46,47].
We found here, that phenols and perfluoro-tert-butyl
alcohol can also be selected as the ‘acidic component’
(cf. [50]) of a fluorous Mitsunobu reaction (Table 3, runs
1
2 and 13).
Due to the access to PhC(CF ) OCH [51] and
3
2
3
PhC(CF ) OCCl [52] ethers, we thought to apply them
3
2
3
as precursors for the synthesis of a novel ‘CF -rich’ com-
3
pound, PhC(CF ) OCF , which is an isomer of the unknown
3
2
3
perfluoro-tert-butyl phenyl ether, PhOC(CF ) . However,
3
3
the results of these efforts will be published later and else-
where.
Fig. 1. Efficacy of the prediction of phase preference for compounds 3–15.
Scheme 4. Mitsunobu ether synthesis coupled with fluorous separation.

J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
203
Table 3
Synthesis of fluorinated ethers: R –OH (or HO–R –OH)þR –X ! R –O–R (or R O–R –OR )
1
1
2
1
2
2
1
2
1
R –OH (1a–e)
2
R –X (2a–eb)
a
1
R –O–R
2
Run
Method
Bp (8C/mmHg)
mp (8C/solvent)
Yield (%)
2
R O–R –OR
1
2
1
2
3
4
5
6
7
8
9
C
C
C
C
C
C
C
6
6
6
6
6
6
6
H
H
H
H
H
H
H
5
5
5
5
5
5
5
C(CF
C(CF
C(CF
C(CF
C(CF
C(CF
C(CF
3
3
3
3
3
3
3
)
)
)
)
)
)
)
2
2
2
2
2
2
2
OH (1a)
OH (1a)
OH (1a)
OH (1a)
OH (1a)
OH (1a)
OH (1a)
CH
CF
3
–OSO CH
2
3
(2a)
A
A
A
B
B
A
B
A
A
B
B
B
B
3aa
3ab
3ac
3ac
3ad
3ae
3ae
3ba
3bb
3be
3ce
3de
3ee
164
<250
85
75
33
b
3
CH –OSO
2
2
CF
3
(2b)
(2ca)
C
7
C
7
C
8
C
8
C
8
F
F
F
F
F
15CH
15CH
17CH
17CH
17CH
2
2
2
2
2
–OSO
2
CF
3
120–129/20
c
c
–OH (2cb)
0
b
d
CH
CH
CH
2
2
2
–OH (2d)
11
CH
CH
2
–I (2ea)
–OH (2eb)
130–131/1
35
88
81
64
61
86
76
91
2
160–168/20
1,3-C
1,3-C
1,3-C
6
6
6
H
4
H
4
H
4
6
[C(CF
[C(CF
[C(CF
3
3
3
)
2
)
2
)
2
OH]
OH]
OH]
2
2
2
(1b)
(1b)
(1b)
CH
CF
3
–OSO CH
2
3
(2a)
CF (2b)
6 14
82–84/C H
3
CH –OSO
2
2
3
120–125/20
39–41/i-octane
180–184/1
165–170/20
224–227
10
11
12
13
C
8
C
8
C
8
C
8
F
F
F
F
17CH
17CH
17CH
17CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
–OH (2eb)
–OH (2eb)
–OH (2eb)
–OH (2eb)
1,3,5-IC
1,3-CF
(CF COH (1e)
H
3
[C(CF
3
)
2
OH]
2
(1c)
2
2
2
3
C
6
H
4
OH (1d)
3 3
)
a
1
2
1
2
Method A (Williamson): R OH þ NaH/DMF, R X at RT then heating. Method B (Mitsunobu): R OH þ R OH, Ph
3 3 6 14
P/DEAD/PhCF at RT, then C F /
CH
3
b
OH partition.
Not determined.
c
No formation of 3ac detected (GC).
d
1
1
Mixture of isomers: Rf8CH
2
CH
2
OR to Rf8CH(OR )CH3 ꢀ 10:1 (GC).
3
. Conclusions
[crosslinked methylsilicone gum] 50 m  0:2 mm  0:5 mm
column, H carrier gas, FID detection).
2
1
. The use of calculated Hildebrand parameters of ‘target
molecules’ and a regression equation fitted to a sizable
database of experimentally determined fluorophilicity
values is a powerful tool for estimation of their phase
preference.
4.1. 2.2.2-Trifluoroethyl trifluoromethanesulfonate (2b)
Yield: 5.34 g(46%)atascaleof50 mmol, colourlessoil, bp
1
9
89–91 8C, prepared asreported [54]. GC:96.2%. F NMR(d,
ppm): (SO )–CF :À74.90 (3F); –CH –CF : À75.19 (3F), t,
2
3
. Mitsunobu and Williamson syntheses were found as
complementary methods for the preparation of novel
generation fluorophilic ethers involving Class III pony-
tails.
. Effective synthetic methods and separation procedures
can be developed or selected, respectively, if the
reaction components’ phasephilicity is understood and
purposefully tuned.
2
3
1
2
3
3
13
J
FÀH
¼ 7:6 Hz. H NMR (d, ppm): 4.63 qa, (7.3 Hz)
C
NMR (d, ppm): CF CH 121.3 qa (278.3 Hz), CF CH
3
2
3
2
68.9 (39.3 Hz), CF SO 118.9 qa (319.6 Hz) MS (EI)
þ
3
2
þ
(m/z, I, MÀX): 200(0.2%)(M À 32) , 163(8.0%)(M À 69) ,
þ
147(6.4%)(M À 85) , 133(18%), 99(22%), 83(34%),
þ
69(100%); MS (CI, isobutane) ðM þ HÞ ¼ 233.
4.2. 2,2,3,3,4,4,5,5,6,6,7,7,8,8-Pentadecafluorooctyl
trifluoromethanesulfonate (2ca)
4
. Experimental details
To an ice-cooled and stirred solution of alcohol 2cb
(12.0 g, 30 mmol) and pyridine (2.91 ml, 36 mmol) in abso-
lute CH Cl (60 ml) trifluoromethanesulfonic anhydride
(6.0 ml, 36 mmol) was added during 1 h. The mixture
was stirred for 1 h at 0 8C, then at room temperature over-
night. After evaporation the residue was partitioned between
ether (150 ml) and ice-water (40 ml). The ether phase was
Most of the compounds (1a, 1b, 1d, 1e, 2cb [Apollo]; 2d
Fluka]) used in this study are either commercially available
[
or can be prepared according to literature examples
2
2
{
PhC(CF ) Cl [53], 3aa [51], 2b [54], 2ca [55], 2ea [56],
3 2
2
eb [57]}. The structures of all new compounds were
confirmed by H-, 13C- and F NMR spectroscopy (Varian
1
19
1
INOVA 400, 400 MHz for H) using TMS and CFCl as
3
dried (MgSO ) and evaporated to give pink oil, which on
4
internal standards in a solvent mixture of 1:1 (v/v) CDCl3
and Freon-113 (CF ClCFCl ). Mass spectra were deter-
mined on a VG ZAB2-SEQ tandem mass spectrometer
using electron impact (70 eV) for ionization and direct
probe for sample introduction at a source temperature of
fractionation yielded 14.6 g (91.5%) colourless liquid of
1
9
2
2
bp :< 100 8C/16 mmHg (cf. [55]). GC: 99.3%. F NMR (d,
ppm): (SO )–CF :À74.81 (3F); –CF –CF : À81.44 (3F); –
2
3
2
3
CH –CF : À120.22 (2F); others: À122.15 (2F); À122.30
2
2
1
(2F); À123.08 (2F); À123.32 (2F); À126.59 (2F). H NMR
3
13
1
80–250 8C. Mass range (m/z) from 25–1500 was consid-
(d, ppm): 4.82 t, ( J
¼ 12:3 Hz) C NMR (d, ppm): CH
FÀH
2
2
1
ered. Fluorophilicities were determined by GC analysis as
reported [27]; (Hewlett-Packard 5890 Series II, PONA
68.4 t ( J
262:0 Hz and
¼ 28:8 Hz), CH CF 113.3 tt ( J
¼
CÀF
2
2
CÀF
2
J
CÀF
¼ 32:6 Hz) CF CF 117.5 qa t
2
3

204
J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
(1
J
¼ 288:0 Hz and J
2
¼ 32:6 Hz), (CF ) 14–106
1
H NMR O–CH 3.89 qa (7.7 Hz), Ar-2H and Ar-6H 7.55 br
2
CÀF
CÀF
2 5
overlapping signals MS(EI) (m/z, I, M À X): 532(0.01%)-
d (7.3 Hz; 2H), Ar-3H and Ar-4H and Ar-5H 7.43-7.47
m(3H), 13C NMR O–CH2 64.2 qa (37.4 Hz), CH CF
123.1 qa (277.3 Hz), C(CF ) O 83.3 sept (28.8 Hz),
þ
þ
þ
(
(
(
(
M) , 513(0.2%)(M À F) , 463(0.7%)(M À CF3) , 361-
þ þ
5 9
2
3
1.1%)(M–171) , 313 (3.5%), 231(0.6%)(C F ) , 219-
3 2
þ
þ
0.8%)(C F ) , 169(2.6%)(C F ) , 163(9.7%), 131(12%)
4
C(CF ) O 122.4 qa (290.8 Hz), Ar-1C 126.9, Ar-2C and
3 2
9
3
7
þ
þ
C F ) , 99(22%), 69(100%)(CF3) . HR-MS (CI, isobutane)
3
Ar-6C 128.4, Ar-3C and Ar-5C 129.5, Ar-4C 131.3. MS (EI)
5
þ
þ
þ
ðM þ HÞ ¼ 532:9544 thus M ¼ 531:9466, calculated for
C H F SO M ¼ 531:9437.
(m/z, I, M À X): 326(37%)(M) , 307(6.1%)(MÀF) ,
þ þ
3
3 2
257(100%)(M À CF ) , 227(7.1%) (M–151, PhC(CF ) ) ,
9
3
18
3
2
07(17%), 177(18%), 175(9.2%), 127(29%), 105(42%),
4
.3. [2,2,2-Trifluoro-1-chloro-1-
trifluoromethyl)ethyl]benzene (Table 4, Entry 3)
83(32%), 77(20%), 69(25). HR-MS (EI): M ¼ 326:0380,
(
calculated for C H F O M ¼ 326:0353.
1
1 7 9
Yield: 76%, colourless oil, bp 154 8C, prepared as
4.7. [2,2,2-Trifluoro-1-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
pentadecafluorooctyloxy)-1-(trifluoromethyl)
ethyl]benzene (3ac)
19
reported [53]. GC: 92%. F NMR (d, ppm): CF :À70.44
3
1
(
s). H NMR Ar-2H and Ar-6H 7.91 br d (7.5 Hz; 2H), Ar-3H
and Ar-4H and Ar-5H 7.51–7.55 br m (3H), 13C NMR
2
C(CF ) 72.9 sept ( JCÀF ¼ 30:7 Hz), C(CF ) Cl 123.7 qa
Yield: 2.08 g (33%) colourless oil, bp: 120–129 8C/20
3
2
3 2
1
9
(286.0 Hz), Ar-1C 129.6, Ar-2C and Ar-6C 129.8 br, Ar-3C
and Ar-5C 130.1, Ar-4C 132.1.
mmHg. GC: 93%. F NMR (d, ppm): (C)–CF : À71.31
3
3
(6F);–CF –CF :À81.40(3F), t, J
¼ 10:1 Hz;CH –CF :
2
3
FÀF
2
2
À120.16 (2F); others: À122.38 (4F); À122.41 (2F);
1
4
.4. General procedure for the synthesis of compounds
aa, 3ab, 3ac, 3ae, 3ba, 3bb (Method A)
À122.44 (2F); À126.63 (2F). H NMR (d, ppm): O–CH
2
3
3
4.13 qa ( J
(
¼ 12:5 Hz), Ar-2H and Ar-6H 77.68 br d
13
FÀH
7.3 Hz; 2H) 7.5–77.6 overlapping m’s (3H). C NMR
To a stirred solution of alcohol 1a (10 mmol) or 1b
5.0 mmol) in absolute DMF (10 ml) pentane washed
sodium hydride (ꢀ0.3 g, ꢀ13 mmol) was added under an
argon atmosphere during 30 min at about À10 to À20 8C
temperature (caution!). After addition of 2a, 2b, 2ca or 2ea
(d, ppm): O–CH 63.5 t (28.8 Hz), C(CF ) O 83.1 sept
2
3 2
(
(29.7 Hz), Ar-1C 126.8, Ar-2C and Ar-6C 128.3 br,
Ar-3C and Ar-5C 129.3, Ar-4C 131.1. HR-MS (EI):
M ¼ 626:0178, calculated for C H F O M ¼ 626:0162.
1
7 7 21
(
12 mmol) to the reaction mixture, it was allowed to warm to
room temperature, then stirred at this temperature for 12 h
2a) or heated at 60 8C for 6 h (2b, 2ca) and for 12 h (2ea).
4.8. [2,2,2-Trifluoro-1-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,-
11,11-heptadecafluoroundecyloxy)-1-(trifluoro-
methyl)ethyl]benzene (3ae)
(
Then, the mixture was added to ice (50 g) and extracted with
ether (3Â 30 ml). The organic phases were combined,
Yields: 2.46 g (35%) colourless oil, bp: 130–131 8C/
1
9
washed with water (2Â 20 ml) and dried (MgSO ). After
1 mmHg. GC: 99.8%. F NMR (d, ppm): (C)–CF :
4
3
3
the solvent had been removed by atmospheric distillation,
the crude product obtained was fractionated in a short path
distillation apparatus. For boiling point and pressure data,
see: Scheme B.
À71.84 (6F); –CF –CF : À81.48 (3F), t, JFÀF ¼ 10:4 Hz;
2
3
–CH –CF : À114.90 (2F); others: À122.04 (2F); À122.24
2
2
1
(4F); À123.08 (2F); À123.80 (2F); À126.60 (2F). H NMR
(d, ppm): O–CH 3.74 t (6.1 Hz), O–CH CH 2.08 tt (8.5 Hz
2
2
2
and 6.1 Hz), CH CF 2.35 tt (18 and 8.5 Hz), Ar-2H and Ar-
6H 7.63 br d (2H) (7.3 Hz), 7.5–7.6 overlapping multiplets
m’s (3H) 13C NMR (d, ppm):, O–CH 65.1, O–CH CH 21.3,
2
2
4
.5. [2,2,2-Trifluoro-1-methoxy-1-
trifluoromethyl)ethyl]benzene (3aa)
(
2
2
2
2
CH CF 27.9 t ( JCÀF ¼ 23:0 Hz), C(CF ) O 83.2 sept
2
2
3 2
Yield: 2.20 g (85%) colourless oil, bp: 164 8C as of [51].
(27.8 Hz), Ar-1C 128.5, Ar-2C and Ar-6C 128.3 br, Ar-3C
and Ar-5C 129.0, Ar-4C 130.5 MS (EI) (m/z, I, MÀX):
1
9
1
GC: 98.2%. F NMR (d, ppm): CF :À71.37 (s). H NMR
3
þ
þ
O–CH 3.53 s (3H), Ar-2H and Ar-6H 7.67 br (2H), Ar-3H
3
704(0.2%)(M) , 635(2.0%) (MÀCF ) , 477(8.8%)(MÀ
3
and Ar-4H and Ar-5H 7.5 m (3H), 13C NMR O–CH 55.5,
227) , 461(3.6%), 441(7.3%), 395(3.9%), 228(34%),
227(60) (PhC(CF ) ) , 208(32%), 207(18%), 175(100%),
þ
3
2
þ
C(CF ) 84.6 sept ( J
CÀF
(290.8 Hz), Ar-1C 129.4, Ar-2C and Ar-6C 19.6, Ar-3C and
Ar-5C 130.1, Ar-4C 131.7.
¼ 27:8 Hz), C(CF ) O 124.0 qa
3 2
3
2
3 2
159(40%), 105(37%), 77(10%), 69(16%), 47(28%). HR-
MS (EI): M ¼ 704:0413, calculated for C H F O
20 11 23
M ¼ 704:0443.
4
.6. [2,2,2-Trifluoro-1-(2,2,2-trifluoroethoxy)-1-
trifluoromethyl)ethyl]benzene (3ab)
(
4.9. 1,3-Bis[1-(methoxy)-2,2,2-trifluoro-1-
(trifluoromethyl)ethyl]benzene (3ba)
Yield: 2.45 g (75%) colourless oil, bp :< 250 8C (bath
temperature). GC: 93%. 19F NMR (d, ppm): (C)–CF :
Yield: 1.78 g (81%) white crystals, mp: 82–84 8C/C H
same as reported [42]. GC: 98.1%. F NMR (d, ppm):
3
6 14
3
19
À71.39 (6F); –CH –CF : À74.92 (3F), t, J
¼ 7:7 Hz.
2
3
FÀH

J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
205
1
CF :À71.42 (s). H NMR (d, ppm): O–CH 3.54 s (3H), Ar-
(1.33 d, CH3; 5.08 qa, CH). The coupling pattern is evi-
denced by 2D COSY. 13C NMR (d, ppm) O–CH 59.0 br,
3
3
2
H 7.93 br s (1H), Ar-4H and Ar-6H 7.78 br d (7.9 Hz) (2H),
2
Ar-5H 7.63 t (8.2 Hz) (1H), 13C NMR (d, ppm): O–CH3
4.2, CF3 122.6 q (288.9 Hz), C(CF ) OCH3 83.3 sept
CH CF 32.0 t (23.0 Hz), C(CF ) O 83.0 sept (27.9 Hz),
2
2
3 2
5
Ar-1C 128.0, Ar-2C and Ar-6C 128.2 br, Ar-3C and Ar-5C
129.1, Ar-4C 130.7. HR-MS (EI): M ¼ 690:0299, calcu-
lated for C H F O M ¼ 690:0286.
3 2
(28.8 Hz), Ar-2C 128.8 br, Ar-1C and Ar-3C 129.5, Ar-4C
and Ar-6C 130.4 br, Ar-5C 129.4.
1
9 9 23
4
(
.10. 1,3-Bis[1-(2.2.2-trifluoroethoxy)-2.2.2-trifluoro-1-
trifluoromethyl)ethyl]benzene (3bb)
4.13. [2,2,2-Trifluoro-1-(4,4,5,5,6,6,7,7,8,8,9,9,-
10,10,11,11,11-heptadecafluoroundecyloxy)-1-
(trifluoromethyl)ethyl]benzene (3ae)
Yield: 1.84 g (64%) colourless oil, bp: 120–125 8C/
2
0 mmHg. GC: 96.4%. 19F NMR (d, ppm): (C)–CF :
Yield: 6.20 g (88%) colourless oil, bp: 160–168 8C/
20 mmHg. GC: 99.8%. (see: Method A).
3
3
À71.40 (12F); –CH –CF : À75.09 (6F), t, JFÀH ¼ 7:1 Hz.
2
3
1
3
H NMR (d, ppm): O–CH 4.03 qa ( JFÀH ¼ 7:6 Hz), Ar-2H
2
8
(
3
2J
.04 br s, Ar-4H and Ar-6H 7.87 br d (7.3 Hz), Ar-4H 7.71 t
4.14. 1,3-Bis[1-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,-
12,12,13,13,13-heptadecafluoroundecyloxy)-2,2,2-
trifluoro-1-(trifluromethyl)ethyl]benzene (3be)
7.33 Hz), 13C NMR (d, ppm): O–CH 64.4 qa ( JCÀF ¼
2
2
6:5 Hz), CH CF 122.7 qa (277.3 Hz), C(CF ) O 82.9 sept
2 3 3 2
(
¼ 29:7 Hz), C(CF ) O 122.1 qa (289.8 Hz), Ar-1C
CÀF
3 2
and Ar-3C 128.9 s, Ar-2C 128.1 br s, Ar-4C and Ar-6C 130.7
br s, Ar-5C 130.1 s. HR-MS (EI): M ¼ 574:0260, calculated
for C H F O M ¼ 574:0237.
Yield: 4.06 g (61%) white crystals, mp: 39–41 8C/i-
1
9
octane. GC: 98.9%. F NMR (d, ppm): (C)–CF : À71.45
3
3
(6F);); –CF –CF : À81.49 (3F), t, JFÀF ¼ 9:9 Hz; –CH –
16
8
18
2
2
3
2
CF : À115.50 (2F); others: À122.20 (2F); 122.39 (4F);
2
1
4
.11. General procedure for the synthesis of compounds
ad, 3ae, 3be, 3ce, 3de, 3ee (Method B)
À123.21 (2F); À123.91 (2F); À126.67 (2F). H NMR (d,
3
ppm): O–CH 3.73 t (6.1 Hz), O–CH CH 2.09 tt (8.8 Hz;
2
2
2
6.1 Hz), CH CF 2.32 tt (17.4 Hz; 8.8 Hz), Ar-2H 7.90 br s,
Ar-4H and Ar-6H 7.77 br d (7.9 Hz), Ar-5H 7.63 t (7.9 Hz).
2 2
The appropriate acidic component 1a, 1d and 1e
10 mmol) or 1b and 1c (5.0 mmol), triphenyl-phosphine
4.10 g, 15.6 mmol) and the perfluoroalkyl-alkanol 2d or 2e,
1
3
(
(
C NMR (d, ppm): O–CH 65.5, O–CH CH 21.3 br,
2
2
2
CH CF 27.8 (23.0 Hz), CF3 122.5 qa (288.9 Hz),
C(CF ) OCH – 83.0 sept (28.8 Hz), Ar-1C and Ar-5C
3 2 2
2
2
respectively, were dissolved in benzotrifluoride (90 ml) with
stirring. Then, the solution was cooled in an ice-bath and
diethyl azodicarboxylate (2.61 g, 15 mmol) dissolved in
benzotrifluoride (10 ml) was added during 30 min. The
mixture was allowed to warm to room temperature and
stirred for 1 h. Then, the solvent was distilled off (bath
temperature < 130 8C) and the residue was partitioned
between perfluoro(2-butyltetrahydrofuran) or perfluorohex-
anes (50 ml) and methanol (50 ml). The fluorous phase was
washed with methanol (2Â 50 ml) and the fluorocarbon
solvent was distilled off at a bath temperature less than
129.6 coalesced lines, Ar-2C 128.1 br, Ar-4C and Ar-6C
130.3 br.
4.15. 3,5-Bis[1-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,-
13,13,13-heptadecafluoroundecyloxy)-2,2,2-trifluoro-1-
(trifluromethyl)ethyl]iodobenzene (3ce)
Yield: 5.90 g (81%) colourless oil, bp: 180–184 8C/
1
9
1 mmHg. GC: 97.6%. F NMR (d, ppm): (C)–CF :
3
3
À71.28 (6F);); –CF –CF : À81.49 (3F), t, JFÀF ¼
2
3
1
30 8C to afford the ‘crude products’ almost free from any
10:1 Hz; –CH –CF : À115.02 (2F); others: À122.11 (2F);
2
2
organic impurities (GC purity > 90%). Further purification
was effected by short path distillation (Raschig rings pre-
vented foaming) or by recrystallization (Scheme B).
À122.33 (4F); À123.15 (2F); À123.84 (2F); À126.68 (2F).
1
H NMR O–CH 3.75 t (6.1 Hz), O–CH CH 2.09 tt (8.3 Hz
2
2
2
and 6.1 Hz), CH CF 2.31 tt (17.1 Hz and 8.3 Hz), Ar-4H
2
2
1
3
7.86 br s (1H), Ar-2Hand AR-6H 8.09 br s (2H). C NMRO–
CH 65.9, O–CH CH 21.3 br, CH CF 27.8 t (21.1 Hz),
4
1
.12. [2,2,2-Trifluoro-1-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,-
0,10-pentadecafluorodecyloxy)-1-(trifluoromethyl)-
2
2
2
2
2
C(CF ) O 82.4 sept (29.7 Hz), CF 122.3 qa (288.9 Hz),
3
2
3
ethyl]benzene and [2,2,2-trifluoro-2-(3,3,4,4,5,5,6,6,7,7,-
,8,9,9,10,10,10-pentadecafluorodecyloxy)-1-
Ar-1C 94.3, Ar-2C and Ar-6C 139.3, Ar-3C and Ar-5C
131.5, Ar-4C 127.3.
8
(
trifluoromethyl)ethyl]benzene (3ad)
4.16. 1-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
Heptadecafluoroundecyloxy)-3-(trifluoromethyl)benzene
(3de)
Yield: 0.76 g (11%) colourless oil. GC: 95% mixture of
1
isomers (10:1). H NMR (d, ppm): O–CH 3.96 t (6.7 Hz),
2
CH CF 2.61 tt (17.7 Hz; 6.7 Hz), Ar-2H and Ar-6H 7.63 br
2
2
d (2H; 77.3 Hz), Ar-3H and Ar-4H and Ar-5H 7.50–7.60
overlapping multiplets. The rearrangement is reflected from
the presence of a CHCH unit detected as an AX signal set
Yield: 4.73 g (76%) colourless oil, bp: 165–170 8C/
1
9
20 mmHg. GC: 94.6%. F NMR (d, ppm): (Ph)–CF :
3
3
À63.51 (3F);); –CF –CF : À81.46 (3F), t, JFÀF ¼
3
3
2
3

206
J. R a´ bai et al. / Journal of Fluorine Chemistry 114 (2002) 199–207
[
[
10] D.P. Curran, S. Hadida, J. Am. Chem. Soc. 118 (1996) 2531.
9
:9 Hz; –CH –CF : À114.86 (2F); others: À122.03 (2F);
2
2
11] A. Studer, S. Hadida, R. Ferritto, S.-Y. Kim, P. Jeger, P. Wipf, D.P.
Curran, Science 275 (1997) 823.
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À122.28 (4F); À123.11 (2F); À123.82 (2F); À126.60 (2F).
1
H NMR (d, ppm): O–CH 4.12 t (5.8 Hz), O–CH CH 2.19
2
2
2
[
3
tt (8.0 and 5.8 Hz), CH CF 2.38 tt ( JHÀF ¼ 18:3 and
2
2
[13] D.P. Curran, Synlett (2001) 1488.
8.0 Hz), Ar-2H 7.19 br s, Ar-4H 7.27 br d (7.9 Hz),
Ar-5H 7.42 t (8.0 Hz), Ar-6H 7.10 dd (8.2 Hz and
[14] Z. Luo, Q. Zhang, Y. Oderaotoshi, D.P. Curran, Science 291 (2001)
1
766.
.2 Hz). 1 C NMR (d, ppm): O–CH2 66.8, O–CH CH
3
[15] L.K. Yeung, R.M. Crooks, Nano Lett. 1 (2001) 14.
2
2
1
2
2
[
16] L.E. Kiss, I. K o¨ vesdi, J. R a´ bai, J. Fluorine Chem. 108 (2001) 95.
17] H. Li, X. Wang, Y. Song, Y. Liu, Q. Li, L. Jiang, D. Zhu, Angew.
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0.9 br, CH CF 28.3 t (23.0 Hz), Ar-1C 159.1, Ar-2C
11.5 qa (3.8 Hz), Ar-3C 132.7 qa (32.6 Hz), Ar-4C and
2
2
[
Ar-6C 118.0 two coalesced lines, Ar-5C 130.2, Ar-CF3
24.2 qa (271.6 Hz). HR-MS (EI): M ¼ 622:0420, calcu-
lated for C H F O M ¼ 622:0412.
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Hochschule Aachen, 1991.
1
[
[
19] Z. Szl a´ vik, G. T a´ rk a´ nyi, Z. Skribanek, E. Vass, J. R a´ bai, Org. Lett. 3
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1
8 10 20
(
4
3
.17. 1-[1,1-Bis(trifluoromethyl)-2,2,2-trifluoroethoxy]-
,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
Inorg. Chem. Commun. 1 (1998) 197.
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J.S. Lin, A. Dobrynin, M. Rubinstein, A.L.C. Burke, J.M.J. Fr e´ chet,
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heptadecafluoroundecane (3ee)
[
[
22] M.P. Krafft, J.G. Riess, Biochimie 80 (1998) 489.
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Yield: 6.33 g (91%) colourless oil, bp: 224–227 8C. GC:
1
9
9
9.8%. F NMR (d, ppm): (C)–CF : À70.97 (9F);); –CF –
3
3 2 2
3
2
CF : À81.47 (3F), t, J
¼ 11:1 Hz; –CH –CF : À114.96
[24] J.C. Giddings, Unified Separation Science, Wiley, New York, 1991.
FÀF
[
[
[
[
25] A.F.M. Barton, CRC Handbook of Solubility Parameters and Other
Cohesion Parameters, CRC Press, Boca Raton, Fl, 1983, pp. 64–66.
26] I.T. Horv a´ th, G. Kiss, R.A. Cook, J.E. Bond, P.A. Stevens, J. R a´ bai,
E.J. Mozeleski, J. Am. Chem. Soc. 120 (1998) 3133.
´
27] Z. Szl a´ vik, G. T a´ rk a´ nyi, A. G o¨ m o¨ ry, G. Tarczay, J. R a´ bai, J. Fluorine
Chem. 108 (2001) 7.
(
2F); others: À122.15 (2F); À122.33 (4F); À123.16 (2F);
19
2
À123.98 (2F); À126.64 (2F). H NMR O–CH 4.17 t
(
2
(
(
5.8 Hz), O–CH CH 2.07 tt (8.0 and 5.8 Hz), CH CF
2 2 2 2
.27 tt (18.3 and 8.0 Hz; 3JHÀF ¼ 18:3 Hz), 13C NMR:
CF ) CO 120.7 qa (292.7 Hz), (CF ) CO 80.2 decett
3
3
3 3
28] B. Richter, E. deWolf, G. van Koten, B.-J. Deelman, J. Org. Chem.
29.7 Hz),O–CH2 68.4 br, O–CH CH2 21.3 br,
2
6
5 (2000) 3885.
[29] M.A. Casado, J. Roovers, S.T. Stobart, Chem. Commun. (2001) 313.
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1999) 849.
CH CF 27.5 t (23.0 Hz), CH CF 118.5 tt (255.3 and
2
2
2
2
þ
3
6
(
1.7 Hz), MS (EI) (m/z, I, M À X): 696(0.6%)(M) ,
þ þ
[
95(1.8%) (M À 1) , 677(2.4%)(MÀF) , 461(15%)
(
þ
þ
MÀ235, M À OC(CF ) ) , 441(38)(MÀ255) , 249(84%)
[31] F.E. Behr, Yu. Cheburkov, J.C. Hansen, D.-W. Zhu, (3M Company)
US Patent 5,427,656 (1995); Chem. Abstr. 123 (1995) 154968s.
3
3
þ
þ
(
CH OC(CF ) ) , 91(61%), 69(27%)(CF ) , 47(100%).
2
3 3
3
[
[
32] Q.S. Zhang, Z.Y. Luo, D.P. Curran, J. Org. Chem. 65 (2000) 8866.
33] L.M. Yagupol’skii, N.V. Kondratenko, N.I. Delyagina, B.L. Dyatkin,
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Acknowledgements
[
[
[
34] N. Takada, T. Abe, A. Sekiya, J. Fluorine Chem. 92 (1998) 167.
35] K.K. Sun, C. Tamborski, J. Fluorine Chem. 17 (1981) 457.
36] Yu.V. Zeifman, L.T. Lantseva, I.L. Knunyants, Izv. Akad. Nauk.
SSSR Ser. Khim. 27 (1978) 2640.
Support from the Hungarian Scientific Research Founda-
tion (Grant No. T 034871), the COST Action D12 ‘Fluorous
medium: a tool for environmentally compatible oxidation
processes’, and the Hungarian Ukrainian Intergovernmental
S & T Co-operation Programme for 2000–2002 is gratefully
acknowledged.
[
37] N.V. Kondratenko, V.I. Popov, A.A. Kolomeitsev, E.P. Saenko, V.V.
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[
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