Macrocyclic ligands with partially fluorinated sidearms: Synthesis and metal ion complexation

Article abstract of DOI:10.1016/S0040-4020(00)00248-9

Derivatives of aza-12-crown-4, aza-15-crown-5, aza-18-crown-6, 1,10- diaza-18-crown-6 and 1,4,8,12-tetraazacyclopentadecane with partially fluorinated substituents attached to nitrogen are prepared. Their efficiencies and selectivities in alkali metal and

Full text of DOI:10.1016/S0040-4020(00)00248-9

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3291±3301
Macrocyclic Ligands with Partially Fluorinated Sidearms:
Synthesis and Metal Ion Complexation
*
Sadik Elshani, Evgeny Kobzar and Richard A. Bartsch
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received 4 February 2000; accepted 21 March 2000
AbstractÐDerivatives of aza-12-crown-4, aza-15-crown-5, aza-18-crown-6, 1,10-diaza-18-crown-6 and 1,4,8,12-tetraazacyclopentadecane
with partially ¯uorinated substituents attached to nitrogen are prepared. Their ef®ciencies and selectivities in alkali metal and silver picrate
extractions from aqueous solutions into chloroform are determined and compared with those of appropriate model compounds. Ionophores
with longer spacers of ±CH2OCH2CH2± and ±CH2CH2OCH2CH2± between the nitrogen atom(s) of the macroring and the per¯uoroalkyl
group(s) exhibit greater extraction ef®ciencies than do analogues with shorter spacers consisting of one or two methylene groups. q 2000
Elsevier Science Ltd. All rights reserved.
Introduction
synthesized a series of mono-, di- and tetra¯uorinated
tetraazacyclotetradecanes (cyclams) and demonstrated that
these ligands form stable Cu(II) and Ni(II) complexes.8
Plenio and Diodone showed that partially ¯uorinated
crown ethers and cryptands prepared from small ¯uorine-
containing building blocks form stable complexes with
Group I metal ions.9 Plenio has published an excellent
review on the coordination chemistry of ¯uorine-containing
ligands, including ¯uoro macrocycles.10
Since Pedersen discovered that cyclic polyether compounds
(crown ethers) possess unique complexation capabilities,
there has been great interest in these compounds as
complexing agents for a wide variety of metal ions.1
Many different modi®cations have been made to probe the
in¯uence of ligand structure on the cation-complexing
properties of crown ethers.2 Although a wide variety of
macrocyclic ligands with different donor atoms and other
substituents have been prepared, only a very limited number
of ¯uorine-containing macrocycles have appeared in the
literature.
Shreeve and coworkers synthesized a series of 18-crown-6
derivatives which contain ¯uorinated side arms.11 That such
macrocycles are capable of forming stable complexes
with lanthanum ion was demonstrated by an X-ray crystal
structure.11
In the ®rst report of per¯uorocrown ethers by Lagow and
coworkers, the compounds were synthesized by direct
¯uorination of the corresponding crown ethers.3 Using the
same approach, they later prepared several other per¯uori-
nated macrocycles.4 These compounds may have some
medical applications as 19F NMR imaging agents5 and
oxygen carriers.4b However, as a result of the strong
electron-withdrawing nature of the CF2 units, the oxygen
atoms in these polyethers no longer exhibit Lewis basicity
and the macrocycles do not form stable metal complexes.6
In a patent, Okahara and coworkers reported the preparation
of ¯uorine-containing azacrown ethers by reaction of
monoaza-15-crown-5, 2-(per¯uorohexyl)ethyl tosylate and
Na2CO3 in dioxane.12 Although it was claimed that such
compounds are useful in ion-selective transport of cations
through liquid membranes, no data were provided. Using a
similar approach, Quici and coworkers synthesized a
cyclam derivative with highly ¯uorinated tails and found
that its copper and cobalt complexes act as catalysts
for hydrocarbon oxidation under ¯uorous biphasic (FB)
conditions.13
Farnham and coworkers prepared partially ¯uorinated
macrocyclic polyethers.7 A remarkable property of such
poly¯uorinated crown ethers is their ability to complex
anions, particularly ¯uoride ion.7a Kimura and coworkers
Macrocyclic ligands with one or more ¯uorine-containing
sidearms have potential applications in metal ion sepa-
rations involving a ¯uorous phase14 or supercritical carbon
dioxide.15
Keywords: ionophores; macrocycles; per¯uoroalkyl compounds;
complexation.
* Corresponding author. Tel.: 11-806-742-3069; fax: 11-806-742-1289;
e-mail: rabartsch@ttu.edu
We now report the preparation of a series of macrocyclic
ligands 1±16 with partially ¯uorinated sidearms attached to
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00248-9

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S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
Figure 1. New macrocyclic ligands with partially ¯uorinated sidearms.
nitrogen (Fig. 1) and the evaluation of their metal ion
complexation behavior. The objective of this research effort
was the preparation of partially ¯uorinated macrocycles
which will possess good solubility in nonpolar, partially
¯uorinated and chloro¯uorinated hydrocarbon solvents or
supercritical carbon dioxide, yet provide strong metal ion
complexing ability. Aza-12-crown-4, aza-15-crown-5, aza-
18-crown-6, and 1,10-diaza-18-crown-6 macrocycles were
selected as starting materials in view of their potential for
facile N-functionalization.16 This strategy allows the intro-
duction of ¯uorine-containing groups at speci®c sites in the
macrocyclic ligands without forming a mixture of isomers.
Also, macrocycles with mixed donor atoms form stable
complexes with a wide variety of metal ions.2c±f,17,18
Results and Discussion
Synthesis of macrocycles with partially ¯uorinated
sidearms
For the preparation of macrocyclic ligands with partially
¯uorinated sidearms, several synthetic approaches were
explored.
The preparation of a ¯uorine-containing azacrown ether by
reaction of aza-15-crown-5 and 2-(per¯uorohexyl)ethyl
tosylate was described in a patent.12 To explore the scope
of this reaction, 1H,1H,2H,2H-per¯uoroalkyl tosylates 19
and 20 and mesylate 21 were synthesized in high yields
by reaction of the corresponding alcohols 17 and 18 and
p-toluenesulfonyl or methanesulfonyl chloride (Scheme 1).
In the next step (Scheme 2), reaction of aza-15-crown-5
(22), partially ¯uorinated tosylate 19 and Na2CO3 in re¯ux-
ing dioxane gave a 39% yield 2 (compared with a reported12
Scheme 1. Synthesis of partially ¯uorinated tosylates and mesylate.
Scheme 2. Synthesis of mono- and diazacrown ethers with RFCH2CH2± sidearms.

S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
3293
Interposition of a longer spacer unit between the nitrogen of
the macroring and the per¯uoroalkyl substituent should
enhance metal ion binding. To this end, partially ¯uorinated
carboxylic acids 26±28 with spacers of ±CH2OCH2± and ±
CH2CH2OCH2± between the per¯uoroalkyl group and
carboxylic acid functionality were prepared (Scheme 3).
Thus, partially ¯uorinated alcohols 24, 18 and 25 were
reacted with NaH and bromoacetic acid in THF at room
temperature to provide partially ¯uorinated carboxylic
acids 26±28 in very good yields (70±96%).
Scheme 3. Synthesis of partially ¯uorinated carboxylic acids.
Reactions of commercially available per¯uorooctanoyl
chloride (29) with aza-15-crown-5 (22) and 1,8-diaza-18-
crown-6 (23) in the presence of Et3N in MeCN gave high
yields of the corresponding macrocyclic amides 30 and 31,
respectively (Scheme 4). Partially ¯uorinated carboxylic
acids 26±28 were converted into the corresponding partially
¯uorinated acid chlorides by reaction with oxalyl chloride in
benzene (Scheme 5). These acid chlorides were reacted with
aza-12-crown-4 (35), aza-15-crown-5 (22), aza-18-crown-6
(33), 1,10-diaza-18-crown-6 (23) and 1,4,8,12-tetraaza-
cyclopentadecane (34) in the presence of Et3N in MeCN
to produce 70±95% yields of the corresponding macro-
cyclic amides 35±39 (Scheme 5), diamides 40±42 and tetra-
mide 43 (Scheme 6). Reduction of 30, 31 and 35±43 with
BH3±THF complex in THF gave corresponding macro-
cyclic ligands 1, 3±7, 9, 12±14 and 16 in high yields
(70±90%). Thus, this approach is demonstrated to be con-
venient and quite general for the N-functionalization of
different azamacrocycles with partially ¯uorinated sub-
stituents.
Scheme 4. Reactions of mono- and diazacrown ethers with per¯uoroocta-
noyl chloride.
58% yield). Analogous reactions of two equivalents of
partially ¯uorinated tosylates 19 and 20 with 1,10-diaza-
18-crown-6 (23) gave only very low yields (14±16%) of
the desired products 10 and 11, respectively. Variation of
the base from Na2CO3 to K2CO3 and changing the solvent
from dioxane to MeCN did not increase the yield. Replace-
ment of the partially ¯uorinated tosylate 20 with the corre-
sponding mesylate 21 failed to enhance the yield of
macrocycle 10. From the reaction of commercially available
1-iodo-1H,1H,2H,2H-per¯uorodecane with 23 and K2CO3
in re¯uxing MeCN, no 10 could be isolated.
In addition to their use in the preparation of macrocyclic
amides described above, partially ¯uorinated carboxylic
acids 27 and 28 can be reduced with BH3±THF in THF at
room temperature to the corresponding partially ¯uorinated
alcohols 44 and 45 as shown in Scheme 7. In view of the
ease of isolation and puri®cation of these alcohols, this
approach is more convenient than one in which the alcohols
24 and 18 would be reacted with base and THP-protected
2-bromoethanol.
The next synthetic strategy for the preparation of macro-
cycles with partially ¯uorinated sidearms involved coupling
of a ¯uorine-containing acid chloride with an azacrown
ether and subsequent reduction of the resultant amide to
an amine. Only per¯uorinated acid chlorides are commer-
cially available. After reduction of the resultant partially
¯uorinated macrocyclic amide there would be only a single
methylene group between the nitrogen of the macroring and
the per¯uoroalkyl group. Therefore the strongly electron-
withdrawing effect of the per¯uoroalkyl group might
diminish the electron density of that potential donor atom.
Penta¯uorobenzyl derivatives of aza-15-crown-5 (22) and
1,10-diaza-18-crown-6 (23) were also prepared (Scheme 8).
Reactions of these azacrown ethers with commercially
available penta¯uorobenzyl bromide and K2CO3 in MeCN
at room temperature gave N-penta¯uorobenzyl aza-15-
crown-5 (8) and di-(N-penta¯uorobenzyl) 1,10-diaza-18-
crown-6 (15) in good yields (60±63%).
Scheme 5. Synthesis of monoazacrown ether amides with partially ¯uorinated sidearms.

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S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
Scheme 6. Synthesis of diazacrown ether diamides and a tetraazamacrocycle tetraamide with partially ¯uorinated sidearms.
variations were probed: (i) the cavity size of the macrocycle;
(ii) the number and type of donor atoms; (iii) the length of
the spacer that separates the nitrogen atoms(s) of the
macroring from the ¯uoroalkyl group(s); and (iv) the nature
of the ¯uorine-containing group (partially ¯uorinated alkyl
or aralkyl).
Scheme 7. Synthesis of partially ¯uorinated alcohols.
The metal cation complexing abilities of partially ¯uori-
nated aza-12-crown-4, aza-15-crown-5 and aza-18-crown-
6 derivatives, partially ¯uorinated 1,10-diaza-18-crown-6
derivatives, and four model compounds (i.e. N-benzyl aza-
15-crown-5,20 N-decyl aza-15-crown-5, N,N0-dibenzyl 1,10-
diaza-18-crown-6,21 N,N0-didecyl 1,10-diaza-18-crown-6)
were assessed by solvent extraction of alkali metal and
silver picrates from aqueous solutions into chloroform.22
The extraction results are presented in Tables 1±4.
To provide model compounds for use in the metal ion
complexation studies, aza-15-crown-5 (22) and 1,10-
diaza-18-crown-6 (23) were N-alkylated by reaction with
1-bromodecane and K2CO3 in MeCN at re¯ux to give 46
and 47, respectively, in high yields (88±93%, Scheme 9).
Compound 47 has been prepared earlier by two other
methods.19
Highest extraction of Na1 normally would be anticipated for
a 15-crown-5 ligand based on its ring size.1,23 In agreement,
the data in Table 1 show the following orders of alkali metal
picrate extraction by the partially ¯uorinated aza-15-crown-
5 derivatives: for 1, Na1.Li1.K1<Rb1<Cs1; for 2,
Identities of the new partially ¯uorinated macrocyclic
1
ligands were con®rmed by IR, H and 19F NMR spectro-
scopy and by combustion analyses.
Alkali metal and silver picrate extractions
Na1.K1<Li1<Rb1<Cs1; and for
4
and 6±8,
Na1.K1.Rb1.Li1<Cs1. Similarly, preferred extraction
of Na1 is noted for two model compounds: for N-decyl aza-
15-crown-5, Na1.K1, Li1<Rb1.Cs1; and for N-benzyl
aza-15-crown-5: Na1.K1.Li1<Rb1.Cs1.
Having accomplished the synthesis of a variety of macro-
cycles with partially ¯uorinated sidearms, we next sought to
investigate the various factors that affect their metal ion
complexation characteristics. The following structural
Scheme 8. Reactions of mono- and diazacrown ethers with penta¯uorobenzyl bromide.

S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
3295
2 show the following alkali metal picrate extraction orders
for partially ¯uorinated compounds 9 and 11±15, as well as
for N,N0-didecyl 1,10-diaza-18-crown-6 and N,N0-dibenzyl
1,10-diaza-18-crown-6: K1.Rb1.Na1.Cs1.Li1.
Partially ¯uorinated macrocycles 12±14 which have longer
spacer units between the macroring and the per¯uoroalkyl
group exhibit greater K1 extraction ef®ciency than do
ligands 9 and 11 which have shorter spacers. The K1 extrac-
tion ef®ciencies of 12±14 are essentially the same as that for
the N,N0-didecyl 1,10-diaza-18-crown-6. The K1 extraction
ef®ciency of N, N0-di(penta¯uorobenzyl) 1,10-diaza-18-
crown-6 (15) is slightly higher than that of N, N0-dibenzyl
1,10-diaza-18-crown-6.
Scheme 9. Synthesis of N-decyl mono- and diazacrown ether compounds.
For the partially ¯uorinated aza-15-crown-5 macrocycles,
the Na1 extraction ef®ciency is enhanced as the length of
the spacer between the nitrogen atom of the macroring and
the per¯uoroalkyl unit is increased: 1p2,4,6, 7.
Extraction ef®ciencies for alkali metal picrates by the
partially ¯uorinated macrocycles 4, 6 and 7 are comparable
with those for N-decyl aza-15-crown-5. Thus the
±CH2OCH2CH2± and ±CH2CH2OCH2CH2± spacers between
the macroring and per¯uoroalkyl moieties are long enough
to effectively attenuate the electron-withdrawing effects of
the per¯uoroalkyl groups. Macrocycle 8 that contains a
penta¯uorobenzyl group exhibits similar selectivity and
ef®ciency for Na1 extraction as do the non-¯uorinated
analog N-benzyl aza-15-crown-5 and partially ¯uorinated
macrocycle 2.
The strong electron-withdrawing property of ¯uorine atoms
in the sidearm is re¯ected in the amide carbonyl stretching
frequencies, nCvO, of 1681, 1659 and 1651 cm21 for
partially ¯uorinated aza-15-crown-5 compounds 30, 36
and 38, respectively, and of 1670, 1659 and 1650 cm21
for partially ¯uorinated 1,10-diaza-18-crown-6 compounds
31, 40 and 41, respectively. For comparison with
compounds in the latter series, nCvO for N,N0-didecanoyl
1,10-diaza-18-crown-6 is 1639 cm21 19b
.
The data presented in Table 3 illustrates the effect of the
macrocycle ring size variation for partially ¯uorinated
azacrown ether compounds 3±5 with
a
common
(±CH2OCH2CH2C7F15) sidearm. The selectivity order for
these three partially ¯uorinated macrocycles are: for 3,
Li1.Rb1.K1<Cs1.Na1; for 4, Na1.K1.Rb1.-
Li1.Cs1; and for 5, K1.Rb1.Na1<Cs1.Li1. Thus,
for each ligand, the best extracted alkali metal cation is
that which would be predicted based on the match between
the cation and ligand cavity diameters.
Based on the metal ion-macroring size compatibility
concept, highest extraction of K1 is anticipated for partially
¯uorinated 1,10-diaza-18-crown-6 derivatives and their
non¯uorinated analogs.1,23 In agreement, the data in Table
Table 1. Alkali metal picrate extractions from aqueous solutions into chloroform by partially ¯uorinated aza-15-crown-5 derivatives 1, 2, 4 and 6±8 and by
relevant model compounds
Ionophore
Picrate extracted (%)
K^
Li^
Na^
Rb^
Cs^
1
2
4
6
7
8
1.2^0.4
3.3^0.3
5.8^0.5
7.2^0.6
1.8^0.7
1.5^0.5
15.5^0.3
7.2^0.7
10.7^0.5
37.7^0.0
48.8 ^1.0
52.6^0.3
56.8^0.5
42.5^0.5
58.3^0.0
35.5^0.5
0.4^0.7
4.0^0.4
25.6^0.3
25.0^0.4
30.7^0.7
5.6^0.5
0.3^0.5
3.1^0.9
11.5^0.9
11.7^0.2
11.9^0.7
3.8^0.5
15.1^0.5
6.8^0.5
0.0^0.5
2.7^0.4
4.6^0.5
4.8^0.3
4.3^0.3
1.0^0.7
11.9^0.5
5.5^0.3
N-decyl aza-15-crown-5
N-benzyl aza-5-crown-5
17.6^0.0
13.5^0.6
Table 2. Alkali metal picrate extractions from aqueous solutions into chloroform by partially ¯uorinated diaza-18-crown-6 derivatives 9 and 11±15 and by
relevant model compounds
Ionophore
Picrate extracted (%)
K^
Li^
Na^
Rb^
Cs^
9
11
12
13
14
15
0.6^0.0
2.9^0.5
5.8^0.7
8.1^0.5
6.6^0.6
1.7^0.6
15.4^0.5
6.8^0.3
2.4^0.6
6.1^0.6
29.5^0.5
46.8^0.5
69.9 ^0.2
73.3^0.6
72.1^0.3
58.9^0.3
69.8^0.2
45.7^0.5
3.9^0.2
15.3^0.2
51.2 ^0.5
52.8^0.0
56.4^0.6
31.4^0.3
11.6^0.9
27.6^0.4
0.2^0.6
3.7^0.6
12.2 ^0.4
13.6^0.5
14.1^0.7
3.4^0.4
15.2 ^0.5
22.1^0.5
22.6^0.5
10.4^0.5
31.9^0.5
10.4^0.7
N,N0-didecyl diaza-18-crown-6
N,N0-dibenzyl diaza-18-crown-6
16.2^0.8
7.2^0.2

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S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
Table 3. Alkali metal picrate extractions from aqueous solutions into
chloroform by aza-12-crown-4, aza-15-crown-5 and aza-18-crown-6
compounds with a common, partially ¯uorinated N-substituent
Additional investigations of the complexing abilities of
these new partially ¯uorinated macrocycles are ongoing in
our laboratory and the results will be reported in due course.
Ionophore
Picrate extracted (%)
K^
Li^
Na^
1.6^0.4
Rb^
Cs^
Conclusions
3
4
5
25.7^0.6
5.8^0.5
3.2^0.5
4.2^0.3
2.9^0.9
4.6^0.5
26.5^0.7 29.5^0.5 84.0^0.2 74.2^0.5 28.2^0.9
A series of N-substituted aza-, diaza-, and tetraazacrown
ethers with partially ¯uorinated substituents has been
48.6^1.1 25.6^0.3 11.6^0.9
synthesized.
Spacer
units
of
±(CH2)n±,
and
±(CH2)nO(CH2)m± separate the nitrogen atom(s) of the
macroring from the per¯uoroalkyl group(s). The metal ion
complexation properties of several of these new macrocyc-
lic ligands have been assessed by solvent extraction of alkali
metal and silver picrates from aqueous solutions into chloro-
form. Macrocycles with longer spacers between the macro-
ring and per¯uoroalkyl group are found to exhibit greater
extraction ef®ciencies than do analogues with shorter
spacers.
It is noted that N-1H,1H-3-oxaper¯uoroundecyl aza-18-
crown-6 (5, Table 3), exhibits a higher K1 extraction
ef®ciency than does its diaza-18-crown-6 analogue 12
(Table 2), while the extraction selectivity order remains
the same. This is in good agreement with observations of
Frensdorff that substitution of N or S for O in 18-crown-6
and dibenzo-18-crown-6 reduces the stability constant for
K1 complexation due a decrease in the negative charge on
the heteroatom.24
Due to their high ¯uorine content and strong metal ion
complexation abilities, these macrocyclic ligands are
expected to have applications in metal ion separations
involving a ¯uorous phase14 or supercritical carbon dioxide.15
Recently Tsukube and coworkers have reported that some
lariat azacrown ether and multi-armed macrocyclic poly-
amine derivatives form strong complexes with Ag1.25
Therefore the af®nity of partially ¯uorinated monoaza,
diaza and tetraaza derivatives toward Ag1 was investigated.
The data in Table 4 shows that partially ¯uorinated 1,10-
diaza-18-crown-6 compounds 11±13 exhibit very high
extraction ef®ciency for Ag1 that is comparable to that for
N,N0-didecyl 1,10-diaza-18-crown-6. The greater Ag1
extraction ef®ciencies of partially ¯uorinated diaza-18-
crown-6 derivatives than for aza-18-crown-6 analogues is
attributed to the presence of the second nitrogen donor atom
in the former. The partially ¯uorinated tetraaza macrocycle
16 exhibited high Ag1 extraction ef®ciency with formation
of a silver mirror.
Experimental
General
Starting materials and solvents were purchased from
commercial sources and used without further puri®cation
unless otherwise noted. Tetrahydrofuran (THF) was
distilled from benzophenone ketyl under nitrogen. Melting
points were determined with a MEL-TEMPe capillary
melting point apparatus and are uncorrected. Infrared spec-
tra were recorded as ®lms deposited from CH2Cl2 solutions
onto NaCl plates. NMR spectra were recorded in CDCl3 or
CD3OCD3 with TMS as the internal standard for 1H (200 or
300 MHz) or CFCl3 as the internal standard for 19F
(282.4 MHz). Thin-layer chromatography was performed
on silica gel 60 F254 plates from Analtech and visualized
by UV irradation and/or iodine vapor. Elemental analyses
were performed by Desert Analytics Laboratory of Tucson,
AZ.
The ¯uorine effect on Ag1 extraction ef®ciency by partially
¯uorinated macrocycles is best assessed for macrocycles 9,
11 and 12 which have the same ring size and the same
per¯uoroalkyl group length, but different spacers between
the macroring and the per¯uoroalkyl moiety. Macrocycle 9
with a single methylene group as the spacer exhibits much
lower Ag1 extraction ef®ciency than does ligand 11, which
has two methylene groups in the spacer. Further elongation
of the spacer to ±CH2OCH2CH2± in ionophore 12 further
enhances the Ag1 extraction ef®ciency.
General procedure for the preparation of 1H,1H,2H,2H-
per¯uoroalkyl tosylates 19 and 20 and mesylates 21
Table 4. Silver picrate extractions from aqueous solutions into chloroform
by partially ¯uorinated monoaza, diaza and tetraaza macrocycles
To an ice-cold stirred solution of the per¯uoro-alcohol 17 or
18 (12 mmol) and Et3N (15 mmol) in CH2Cl2 (20 mL) was
added dropwise a solution of p-toluenesulfonyl or methane-
sulfonyl chloride (12 mmol) in 20 mL of CH2Cl2. After
addition was complete (30 min), the reaction mixture was
allowed to come to room temperature and stirring was
continued overnight. The CH2Cl2 solution was washed
with water, dried over MgSO4 and evaporated in vacuo to
give a white solid which was recrystallized from MeOH.
Ionophore
Picrate extracted (%)
4
5
9
11
12
13
83.9^0.5
81.4^0.2
37.7^0.8
91.0^0.5
93.9^0.3
97.4^0.5
83.1^0.3
93.1^0.3a
76.7^0.3
95.1^1.3
15
16
N-decyl aza-15 crown-5
1,10-
1H,1H,2H,2H-Per¯uorooctyl tosylate (19). 91% yield of
white solid with mp 70±718C. H NMR (CDCl3): d 2.46
N,N0-didecyl
diaza-18-crown-6
1
(s1m, 5H), 4.30 (t, 2H, Jˆ6 Hz), 7.38 (d, 2H, Jˆ8 Hz),
a A silver mirror was formed.
8.82 (d, 2H, Jˆ8 Hz). 19F NMR (CDCl3): d 281.2 (s, 3F),

S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
3297
2113.9 to 2114.2 (m, 2F), 2123.4 (s, 2F), 2124.1 (s, 2F),
125.0 (s, 2F), 2126.6 to 2126.7 (m, 2F). Anal. calcd for
C15H11F13O3S: C, 34.76; H, 2.14. Found: C, 34.44; H, 2.01.
stirred for 1 h at room temperature and a solution of
12.0 mmol of bromoacetic acid dissolved in 30 mL of
THF was added dropwise over a period of 1 h. The mixture
was stirred for 24 h and then the excess NaH was destroyed
by careful addition of water. The THF was evaporated in
vacuo. To the residue, 50 mL of water was added and the
aqueous mixture was acidi®ed with aqueous 6 N HCl and
extracted with CH2Cl2. The combined CH2Cl2 extracts were
washed with water, dried over Na2SO4 and evaporated in
vacuo. The crude product was recrystallized from hexanes
to give a white solid.
1H,1H,2H,2H-Per¯uorodecyl tosylate (20). 89% yield of
white solid with mp 49±508C. H NMR (CDCl3): d 2.47
1
(s1m, 5H), 4.30 (t, 2H, Jˆ6 Hz), 7.38 (d, 2H, Jˆ8 Hz),
7.82 (d, 2H, Jˆ8 Hz). 19F NMR (CDCl3): d 281.2 (s, 3F),
2114.0 (s, 2F), 2122.2 to 2122.4 (m, 6F), 2123.2 (s, 2F),
2124.0 (s, 2F), 2126.5 to 2126.6 (m, 2F). Anal. calcd for
C17H11F17O3S: C, 33.02; H, 1.79. Found: C, 33.02; H, 1.94.
1H,1H,2H,2H-Per¯uorodecyl mesylate (21). 92% yield of
1H,1H-Per¯uorooctyloxyacetic acid (26). 96% yield of
white solid with mp 55±568C. IR (NaCl plate): 3510±
1
white solid with mp 72±738C. H NMR (CDCl3): d 2.53±
2.70 (m, 2H), 3.07 (2, 3H), 4.53 (t, 2H, Jˆ6 Hz). 19F NMR
(CDCl3): d 281.3 (s, 3F), 2114.0 to 2114.2 (m, 2F),
2122.2 to 2122.4 (m, 6F), 2123.2 (s, 2F), 2124.0 (s,
2F), 2126.6 to 2126.7 (m, 2F). Anal. calcd for
C11H7F17O3S: C, 24.36; H, 1.30. Found: C, 23.95; H, 0.92.
2855 (COOH), 1728 (CvO) cm21. H NMR (CDCl3): d
1
4.13 (t, 2H, Jˆ14 Hz), 4.32 (s, 2H). 19F NMR (CDCl3): d
281.0 (s, 3F), 2120.1 to 2120.2 (m, 2F), 2122.3 (s, 4F),
2123.0 (s, 2F), 2123.6 (s, 2F), 2126.3 to 2126.4 (m, 2F).
Anal. calcd for C10H5F15O3: C, 26.22; H, 1.10. Found: C,
26.16; H, 0.97.
General procedure for the preparation of partially
¯uorinated macrocycles 10 and 11
1H,1H,2H,2H-Per¯uorodecyloxyacetic acid (27). 70%
yield of white solid with mp 47±488C. IR (NaCl plate):
3500±2850 (COOH), 1734 (CvO) cm21
.
1H NMR
A mixture of 1.05 g (4.0 mmol) of 1,10-diaza-18-crown-6,
8.0 mmol of the per¯uoroalkyl tosylate (19 or 20), Na2CO3
(0.85 g, 8.0 mmol) and 30 mL of dioxane was re¯uxed
under nitrogen for 48 h. After cooling to room temperature,
water was added and the dioxane evaporated in vacuo. The
aqueous mixture was extracted with CH2Cl2. The CH2Cl2
extracts were combined, dried over Na2SO4 and evaporated
in vacuo. The residue was puri®ed by column chroma-
tography on silica gel with CH2Cl2 (to remove the unreacted
per¯uoroalkyl tosylate) and then with EtOAc as eluents.
The EtOAc fractions were combined and evaporated in
vacuo to give a white solid, which was recrystallized from
MeOH.
(CDCl3): d 1.66±2.05 (m, 2H), 3.34 (t, 2H, Jˆ6 Hz), 3.65
(s, 2H). 19F NMR (CDCl3): d 281.0 (s, 3F), 2113.5 to
2113.8 (m, 2F), 2122.0 to 2122.2 (m, 6F), 2123.0 (s,
2F), 2123.9 (s, 2F), 2126.3 to 2126.4 (m, 2F). Anal.
calcd for C12H7F17O3: C, 27.60; H, 1.35. Found: C, 27.64;
H, 1.37.
1H,1H,2H,2H-Per¯uorododecyloxyacetic acid (28). 86%
yield of white solid with mp 95±968C. IR (NaCl plate):
3550±2835 (COOH), 1732 (CvO) cm21
.
1H NMR
(acetone-d6): d 2.40±2.58 (m, 2H), 3.73 (t, 2H, Jˆ8 Hz),
4.16 (s, 2H). 19F NMR (acetone-d6): d 281.2 (s, 3F),
2113.3 (s, 2F), 2121.8 (s, 10F) 2122.8 (s, 2F), 2123.7
(s, 2F), 2126.3 (s, 2F). Anal. calcd for C14H7F21O3: C,
27.02; H, 1.13. Found: C, 26.77; H, 0.92.
N,N0-Bis(1H,1H,2H,2H-Per¯uorooctyl
crown-6 (10). 14% yield of ¯uffy white solid with mp
1,10-diaza-18-
1
60±628C. H NMR (CDCl3): d 2.14±2.41 (m, 4H), 2.79
(t, 8H, Jˆ6 Hz), 2.73 (t, 4H, Jˆ8 Hz), 3.58±3.63 (m,
16H). 19F NMR (CDCl3): d 281.3 (s, 6F), 2114.4 to
2114.6 (m, 4F), 2122.4 (s, 4F), 2123.4 (s, 4F), 2124.0
(s, 4F), 2126.6 to 2126.7 (m, 4F). Anal. calcd for
C28H32F26N2O4: C, 35.23; H, 3.38; N, 2.93. Found: C,
35.23; H, 3.25, N, 2.93.
General procedure for the preparation of partially
¯uorinated macrocyclic amides 30, 31 and 35±43
To a solution of the partially ¯uorinated carboxylic acid 26±
28 (6.0 mmol) in benzene (15 mL) at 08C under nitrogen,
oxalyl chloride (25 mmol) was added dropwise. The
reaction mixture was stirred at room temperature for 1 h,
heated at 608C for 1 h and evaporated in vacuo to give the
corresponding acid chloride which was used immediately
in the next step. (Per¯uorooctanoyl chloride 29 is commer-
cially available.)
N,N0-Bis(1H,1H,2H,2H-Per¯uorodecyl 1,10-diaza-18-
crown-6 (11). 16% yield of ¯uffy white solid with mp
60±628C. H NMR (CDCl3): d 2.15±2.43 (m, 4H), 2.79
1
(t, 8H, Jˆ6 Hz), 2.89 (t, 4H, Jˆ8 Hz), 3.57±3.62 (m,
16H). 19F NMR (CDCl3): d 281.2 (s, 6F), 2114.3 to
2114.6 (m, 4F), 2122.4 (s, 12F), 2123.2 (s, 4F), 2123.9
(s, 4F), 2126.6 (s, 4F). Anal. calcd for C32H32F34N2O4: C,
33.29; H, 2.79; N, 2.42. Found: C, 32.87; H, 2.84; N, 2.49.
The aza macrocycles (6.0 mmol for monoazacrown ethers,
3.0 mmol for diazacrown ethers, and 1.5 mmol for the tetra-
aza macrocycle) and Et3N (6.0 mmol) were dissolved in
MeCN (15 mL) and the solution was cooled to O8C. An
MeCN solution of the acid chloride was added dropwise
during a period of 30 min. The mixture was allowed to
warm to room temperature and stirring was continued over-
night. The mixture was evaporated in vacuo and the residue
was dissolved in EtOAc. This solution was washed with
0.6 N HCl, water, 0.6 M aq NaHCO3 and water, dried
over Na2SO4 and evaporated in vacuo to produce the
General procedure for the preparation of partially
¯uorinated carboxylic acids 26±28
To a mixture of NaH (0.86 g, 36 mmol) and 30 mL of dry
THF under nitrogen, a solution of 6.0 mmol of per¯uoro-
alcohol 24, 18 or 25 dissolved in 30 mL of dry THF was
added dropwise over a 30 min period. The mixture was

3298
S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
partially ¯uorinated macrocyclic amide. (Although macro-
cyclic amides 30, 31 and 35±43 were not submitted for
combustion analysis, satisfactory combustion analysis
results were obtained for each macrocycle that was prepared
by the reduction of these precursors.)
diaza-18-crown-6 (40). 95% yield of white solid with mp
1
76±778C. IR (NaCl plate): 1659 (CvO) cm21. H NMR
(CDCl3): d 3.45±3.64 (m, 24H), 4.13 (t, 4H, Jˆ14 Hz),
4.40 (s, 4H). 19F NMR (CDCl3): d 281.2 (s, 6F), 2120.4
(s, 4F), 2122.5 (s, 8F), 2123.2 (s, 4F), 2123.8 (s, 4F),
2126.6 (s, 4F).
N-Per¯uorooctanoyl aza-15-crown-5 (30). 92% yield of
1
yellowish oil. IR (NaCl plate): 1681 (CvO) cm21. H
N,N0-Bis(2H,2H,4H,4H,5H,5H-3-Oxaper¯uorotridecanoyl
1,10-diaza-18-crown-6 (41). 83% yield of white solid with
mp 63±658C. IR (NaCl plate): 1650 (CvO) cm21. 1H NMR
(CDCl3): d 2.21±2.54 (m, 4H), 3.36±3.45 (m, 24H), 3.65 (t,
4H, Jˆ8 Hz), 4.05 (s, 4H). 19F NMR (CDCl3): d 281.2 (s,
6F), 2113.8 to 2114.0 (m, 4F), 2122.4 (s, 12F), 2123.2 (s,
4F), 2124.1 (s, 4F), 2126.6 (s, 4F).
NMR (CDCl3): d 3.63±3.71 (m, 20H). 19F NMR (CDCl3):
d 280.9 (s, 3F), 2111.2 to 2111.3 (m, 2F), 2120.5 to
2120.9 (m, 4F), 2122.7 (s, 2F), 2122.8 (s, 2F), 2126.2
to 2126.4 (m, 2F).
N,N0-Bis(Per¯uorooctanoyl 1,10-diaza-18-crown-6 (31).
86% yield of white solid with mp 72±748C. IR (NaCl
1
plate): 1670 (CvO) cm21. H NMR (CDCl3): d 3.56±
N,N0-Bis(2H,2H,4H,4H-3-Oxaper¯uoropentadecanoyl 1,10-
diaza-18-crown-6 (42). 78% yield of white solid with mp
3.76 (m, 24H). 19F NMR (CDCl3): d 280.8 (s, 6F),
2111.0 to 2111.2 (m, 4F), 2120.5 to 2120.9 (m, 8F),
2122.1 (s, 4F), 2122.7 (s, 4F), 2126.1 to 2126.3 (m, 4F).
1
79±818C. IR (NaCl plate): 1650 (CvO) cm21. H NMR
(CDCl3): d 2.38±2.56 (m, 4H), 3.55±3.64 (m, 24H), 3.84
(t, 4H, Jˆ8 Hz), 4.23 (s, 4H). 19F NMR (CDCl3): d 281.3
(s, 6F), 2113.9 (s, 4F), 2122.3 (s, 20F), 2123.2 (s, 4F),
2124.1 (s, 4F), 2126.6 (s, 4F).
N-2H,2H,4H,4H-3-Oxaper¯uoroundecanoyl aza-12-crown-
4 (35). 78% yield of yellowish oil. IR (NaCl plate): 1657
1
(CvO) cm21. H NMR (CDCl3): d 3.40 (t, 2H, Jˆ6 Hz),
3.52 (t, 2H, Jˆ6 Hz), 3.57±3.66 (m, 8H), 3.76 (t, 2H,
Jˆ6 Hz), 3.98 (t, 2H, Jˆ6 Hz), 4.13 (t, 2H, Jˆ15 Hz),
4.52 (s, 2H). 19F NMR (CDCl3): d 281.3 (s, 3F), 2120.4
to 2120.6 (m, 2F), 2122.6 (s, 4F), 2123.3 (s, 2F), 2123.9
(s, 2F), 2126.7 (s, 2F).
N,N0,N00,N000-Tetra-(2H,2H,4H,4H-3-Oxaper¯uoroundeca-
noyl 1,4,8,12-tetraazacyclo-pentadecane (43). 78% of
white solid with mp 102±1048C. IR (NaCl plate): 1651
(CvO) cm21 1H NMR (acetone-d6): d 1.49±1.72 (m,
.
6H), 3.08±3.50 (m, 16H), 4.16±4.54 (m, 16H). 19F NMR
(acetone-d6): d 280.8 (s, 12F), 2119.6 (s, 8F), 2121.8 (s,
6F), 2122.5 (s, 8F), 2122.9 (s, 8F), 2126.0 (s, 8F).
N-2H,2H,4H,4H-3-Oxaper¯uoroundecanoyl aza-15-crown-
5 (36). 85% yield of yellowish oil. IR (NaCl plate): 1659
1
(CvO) cm21. H NMR (CDCl3): d 3.46 (t, 2H, Jˆ6 Hz),
General procedure for the reduction of macrocyclic
amides 30, 31 and 35±43 to form the corresponding
macrocyclic amines 1, 3±7, 9, 12±14 and 16
3.56±3.72 (m, 16H), 3.81 (t, 2H, Jˆ6 Hz), 4.15 (t, 2H,
Jˆ14 yHz), 4.43 (s, 2H). 19F NMR (CDCl3): 280.9 (s,
3F), 2120.1 to 2120.2 (m, 2F), 2122.2 (s, 4F), 2122.9
(s, 2F), 2123.4 (s, 2F), 2126.2 to 2126.3 (m, 2F).
A solution containing the macrocyclic amide (30, 31, 35±
43) (4.0 mmol for the azacrown ether derivatives, 2.0 mmol
for the diazacrown ether derivatives and 1.0 mmol for the
tetraaza macrocycle derivative) in 30 mL of dry THF was
cooled at 08C under nitrogen and 30 mL of BH3±THF
(1.0 M solution in THF) was added dropwise over a period
of 30 min. The cooling bath was removed and the reaction
mixture was kept at room temperature for 30 min and then
re¯uxed overnight. The solution was cooled to 08C and
excess borane was destroyed by the addition of water. The
THF was evaporated in vacuo and the white solid
obtained was dissolved in HCl±H2O±MeOH (6:9:30 mL)
and re¯uxed for 8 h. The mixture was evaporated in vacuo
and the residue was treated with a strongly alkaline
solution and extracted with CH2Cl2. The CH2Cl2 extracts
were dried over Na2SO4 and evaporated in vacuo. The
crude product was puri®ed by column chromatography on
silica gel with CH2Cl2 and then EtOAc as eluents for macro-
cycles 1, 3±7, 9 and 16 and by recrystallization from MeOH
for ionophores 9 and 12±14.
N-2H,2H,4H,4H-3-Oxaper¯uoroundecanoyl aza-18-crown-
6 (37). 71% yield of colorless oil. IR (NaCl plate): 1659
1
(CvO) cm21. H NMR (CDCl3): d 3.56 (t, 2H, Jˆ6 Hz),
3.62±3.68 (m, 20H), 3.74 (t, 2H, Jˆ6 Hz), 4.10±4.15 (t, 2H,
Jˆ15 Hz), 4.47 (s, 2H). 19F NMR (CDCl3) d 281.3 (s, 3F),
2120.4 to 2120.5 (m, 2F), 2122.6 (s, 4F), 2123.3 (s, 2F),
2123.8 (s, 2F), 2126.6 to 2126.7 (m, 2F).
N-2H,2H,4H,4H,5H,5H-3-Oxaper¯uorotridecanoyl aza-
15-crown-5 (38). 84% yield of yellowish oil. IR (NaCl
1
plate): 1651 (CvO) cm21. H NMR (CDCl3): d 2.36±
2.58 (m, 2H), 3.46 (t, 2H, Jˆ6 Hz), 3.58±3.72 (m, 18H),
3.65 (t, 2H, Jˆ6 Hz), 4.27 (s, 2H). 19F NMR (CDCl3): d:
281.0 (s, 3F), 2113.5 to 2113.7 (m, 2F), 2121.9 to
2122.2 (m, 6F), 2122.9 (s, 2F), 2123.8 (s, 2F), 2126.2
to 2126.4 (m, 2F).
N-2H,2H,4H,4H,5H,5H-3-Oxaper¯uoropentadecanoyl
aza-15-crown-5 (39): 70% yield of an oil that solidifed on
1
standing. IR (NaCl plate): 1650 (CvO) cm21. H NMR
(acetone-d6): d 2.47±2.64 (m, 2H), 3.46 (q, 4H, Jˆ6 Hz),
3.54±3.65 (m, 14H), 3.75 (t, 2H, Jˆ6 Hz), 4.28 (s, 2H). 19F
NMR (acetone-d6): d 281.4 (s, 3F), 2113.5 (s, 2F), 2122.1
(s, 10F), 2123.0 (s, 2F), 2123.9 (s, 2F), 2126.5 (s, 2F).
N-1H,1H-Per¯uorooctyl aza-15-crown-5 (1). 90% yield
of yellowish oil. 1H NMR (CDCl3): d 3.00 (t, 4H,
Jˆ6 Hz), 3.36 (t, 2H, Jˆ15 Hz), 3.59±3.69 (m, 16H). 19F
NMR (CDCl3): d 281.4 (s, 3F), 2117.5 (s, 2F), 2122.4 to
2122.7 (m, 4F), 2123.4 (s, 2F), 2124.1 (s, 2F), 2126.7 to
2126.8 (m, 2F). Anal. calcd for C18H22F15NO4´0.3CH2Cl2:
N,N0-Bis(2H,2H,4H,4H-3-Oxaper¯uoropentadecanoyl 1,10-

S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
3299
C, 35.06; H, 3.63; N, 2.23. Found: C, 34.97; H, 3.45; N,
2.03.
2126.7 (m, 4F). Anal. calcd for C32H36F30N2O6: C, 34.48;
H, 3.25; N, 2.51. Found: C, 34.56; H, 3.31; N, 2.47.
N-1H,1H,2H,2H,4H,4H-3-Oxaper¯uoroundecyl aza-12-
crown-4 (3). 85% yield of yellowish oil. 1H NMR
(CDCl3): d 2.73±2.79 (m, 6H), 3.62±3.78 (m, 14H), 4.01
(t, 4H, Jˆ15 Hz). 19F NMR (CDCl3): d 281.2 (s, 3F),
2120.1 to 2120.2 (m, 2F), 2122.6 (s, 4F), 2123.4 (s,
2F), 2123.8 (s, 2F), 2126.6 (s, 2F). Anal. calcd for
C18H22F15NO4: C, 35.95; H, 3.68; N, 2.33. Found: C,
36.04; H, 3.62; N, 2.09.
N,N0-Bis(1H,1H,2H,2H,4H,4H,5H,5H-3-Oxaper¯uoro-
tridecyl 1,10-diaza-18-crown-6 (13). 81% of white solid
with mp 49±508C. 1H NMR (CDCl3): d 2.32±2.45 (m, 4H),
2.76 (t, 4H, Jˆ6 Hz), 2.84 (t, 8H, Jˆ6 Hz), 3.51 (t, 4H,
Jˆ6 Hz), 3.56±3.62 (m, 16H), 3.72 (t, 4H, Jˆ6 Hz). 19F
NMR (CDCl3): d 281.0 (s, 6F), 2113.6 to 2113.8 (m,
4F), 2122.0 to 2122.2 (m, 12F), 2123.0 (s, 4F), 2123.9
(s, 4F), 2126.3 to 2126.4 (m, 4F). Anal. calcd for
C36H40F34N2O6: C, 34.79; H, 3.24; N, 2.25. Found: C,
34.68; H, 3.24; N, 2.13.
N-1H,1H,2H,2H,4H,4H-Per¯uoroundecyl aza-15-crown-
5 (4). 88% yield of yellowish oil. H NMR (CDCl3): d
1
2.78±2.83 (m, 6H), 3.61±3.72 (m, 18H), 4.00 (t, 2H,
Jˆ15 Hz). 19F NMR (CDCl3): d 280.9 (s, 3F), 2119.7 to
2119.9 (m, 2F), 2122.2 (s, 4F), 2122.9 (s, 2F), 2123.5 (s,
2F), 2126.2 (s, 2F). Anal. calcd for C20H26F15NO5: C,
37.22; H, 4.06; N, 2.17. Found: C, 37.67; H, 4.20; N, 2.09.
N,N0-Bis(1H,1H,2H,2H,4H,4H,5H,5H-3-Oxaper¯uoro-
pentadecyl 1,10-diaza-18-crown-6 (14). 70% of white
solid with mp 75±768C. H NMR (CDCl3): d 2.30±2.47
1
(m, 4H), 2.76 (t, 4H, Jˆ6 Hz), 2.84 (t, 8H, Jˆ6 Hz), 3.54
(t, 4H, Jˆ6 Hz), 3.58±3.62 (m, 16H), 3.71 (t, 4H, Jˆ6 Hz).
19F NMR (CDCl3): d 281.0 (s, 6F), 2113.7 (s, 4F), 2122.0
(s, 20F), 2123.0 (s, 4F), 2123.9 (s, 4F), 2126.4 (s, 4F).
Anal. calcd for C40H40F42N2O6: C, 33.30; H, 2.79; N, 1.94.
Found: C, 33.26; H, 2.85; N, 1.87.
N-1H,1H,2H,2H,4H,4H-3-Oxaper¯uoroundecyl aza-18-
crown-6 (5). 86% yield of yellowish oil. 1H NMR
(CDCl3): d 2.78±2.84 (m, 6H), 3.59±3.71 (m, 22H), 3.99
(t, 2H, Jˆ15 Hz). 19F NMR (CDCl3): d 281.2 (s, 3F),
2120.0 to 2120.1 (m, 2F), 2122.5 (s, 4F), 2123.2 (s,
2F), 2123.8 (s, 2F), 2126.5 to 2126.6 (m, 2F). Anal.
calcd for C22H30F15NO6: C, 38.32; H, 4.38; N, 2.03.
Found: C, 38.09; H, 4.46; N, 2.04.
N,N0,N00,N000-Tetra(1H,1H,2H,2H,4H,4H-3-Oxaper¯uoro-
undecyl 1,4,8,12-tetraaza-cyclopentadecane (16). 76%
yield of colorless oil. H NMR (CDCl3): d 1.55 (q, 6H,
1
Jˆ6 Hz), 2.48±2.56 (m, 20H), 2.66 (q, 4H, Jˆ6 Hz),
3.63±3.78 (m, 8H), 3.95 (t, 8H, Jˆ16 Hz).). 19F NMR
(CDCl3): d 281.0 to 281.2 (m, 12F), 2119.8 to 2120.0
(m, 8F), 2122.4 (s, 6F), 2123.1 (s, 8F), 2123.7 (s, 8F),
2126.5 to 2126.6 (m, 8F). Anal. calcd for
C51H46F60N4O4´0.6H2O: C, 31.74; H, 2.46; N, 2.90.
Found: C, 31.36; H, 2.57 N, 2.96.
N-1H,1H,2H,2H,4H,4H,5H,5H-Per¯uorotridecyl aza-15-
crown-5 (6). 81% yield of yellowish oil. 1H NMR
(CDCl3): d 2.27±2.52 (m, 2H), 2.75±2.84 (m, 6H), 3.55
(t, 2H, Jˆ6 Hz), 3.62±3.69 (m, 16H), 3.72 (t, 2H,
Jˆ6 Hz). 19F NMR (CDCl3): d 280.9 (s, 3F), 2113.5 to
2113.7 (m, 2F), 2121.9 to 2122.1 (m, 6F), 2122.9 (s, 2F),
2123.8 (s, 2F), 2126.3 (s, 2F). Anal. calcd for
C22H28F17NO5: C, 37.24; H, 3.97; N, 1.97. Found: C,
37.61; H, 4.02; N, 1.71.
General procedure for the reduction of partially
¯uorinated carboxylic acids 27 and 28 to the
corresponding alcohols 44 and 45
N-1H,1H,2H,2H,4H,4H,5H,5H-Per¯uorotricecyl aza-15-
crown-5 (7). 79% yield of yellowish oil. 1H NMR (CDCl3):
d 2.30±2.48 (m, 2H), 2.74±2.84 (m, 6H), 3.55 (t, 2H,
Jˆ6 Hz), 3.61±3.74 (m, 16H), 3.99 (t, 2H, Jˆ6 Hz). 19F
NMR (CDCl3): d 281.2 (s, 3F), 2114.0 (s, 2F), 2122.2
(s, 10F), 2123.2 (s, 2F), 2124.1 (s, 2F), 2126.6 (s, 2F).
Anal. calcd for C24H28F21NO5: C, 33.21; H, 3.36; N, 1.53.
Found: C, 33.02; H, 2.91; N, 1.13.
At 08C under nitrogen, BH3±THF (1.0 M solution in THF,
15 mL) was slowly added to a solution of 3.0 mmol of the
carboxylic acid 27 or 28 in 15 mL of THF. The solution was
stirred at room temperature overnight and the excess borane
was destroyed by the addition of water. The aqueous phase
was saturated with K2CO3. THF was evaporated in vacuo
from the mixture and the aqueous residue was extracted
with CH2Cl2. The combined CH2Cl2 extracts were washed
with water, dried over Na2SO4 and evaporated in vacuo.
N,N0-Bis(1H,1H-Per¯uorooctyl 1,10-diaza-18-crown-6
(9). 80% yield of white solid with mp 52±538C. H NMR
1
1H,1H,2H,2H,4H,4H-3-Oxaper¯uoroundecan-1-ol (44).
The crude product was puri®ed by column chromatography
on silica gel with CH2Cl2 then EtOAc as eluents to give a
colorless oil in 96% yield. IR (NaCl plate): 3373±2855
(CDCl3): d 2.99 (t, 8H, Jˆ6 Hz), 3.43 (t, 4H, Jˆ18 Hz),
3.58±3.64 (m, 16H). 19F NMR (CDCl3): d 281.3 (s, 6F),
2118.0 to 2118.3 (m, 4F), 2122.3 (s, 8F), 2123.3 (s, 4F),
2124.1 (s, 4F), 2126.7 to 2126.8 (m, 4F). Anal. calcd for
C28H28F30N2O4: C, 32.76; H, 2.75; N, 2.73. Found: C, 32.74;
H, 2.71; N, 2.77.
1
(OH) cm21. H NMR (CDCl3): d 3.76±3.97 (m, 4H), 4.06
(t, 2H, Jˆ10 Hz). 19F NMR (CDCl3): d 281.0 (s, 3F),
2119.8 to 2119.9 (m, 2F), 2122.2 to 2122.3 (m, 4F),
2122.9 (s, 4F), 2123.5 (s, 4F), 2126.3 to 2126.4 (m,
2F). Anal. calcd for C10H7F15O2: C, 27.04; H, 1.59.
Found: C, 27.08; H, 1.42.
N,N0-Bis(1H,1H,2H,2H,4H,4H-3-Oxaper¯uoroundecyl
1,10-diaza-18-crown-6 (12). 80% yield of yellowish oil. 1H
NMR (CDCl3): d 2.77±2.84 (m, 12H), 3.57±3.61 (m, 16H),
3.69 (t, 4H, Jˆ6 Hz), 3.98 (t, 4H, Jˆ15 Hz). 19F NMR
(CDCl3): d 281.2 (s, 6F), 2120.0 to 2120.2 (m, 4F),
2122.6 (s, 8F), 2123.2 (s, 4F), 2123.8 (s, 4F), 2126.5 to
1H,1H,2H,2H,4H,4H,5H,5H-3-Oxaper¯uorotridecan-1-
ol (45). Recrystallization from hexanes gave a white solid
with mp 29±308C in 79% yield. IR (NaCl plate): 3390 (OH)

3300
S. Elshani et al. / Tetrahedron 56 (2000) 3291±3301
1
cm21. H NMR (CDCl3): d 2.33±2.52 (m, 2H), 3.56±3.61
(m, 2H), 3.69±3.83 (m, 4H). 19F NMR (CDCl3): d 281.3 to
281.6 (m, 3F), 2113.9 to 2114.1 (m, 2F), 2122.3 to
2122.5 (m, 6F), 2123.3 (s, 2F), 2124.2 (s, 4F), 2126.7
to 2126.8 (m, 2F). Anal. calcd for C12H9F17O2: C, 28.36; H,
1.78. Found: C, 28.29; H, 1.50.
1.42 (m, 4H), 2.46 (q, 4H, Jˆ8 Hz), 2.76 (t, 8H, Jˆ6 Hz),
3.57±3.63 (m, 16H). Anal. calcd for C32H66N2O4: C, 70.79;
H, 12.25; N, 5.16. Found: C, 70.82; H, 12.46; N, 5.33.
Alkali metal picrate extraction
Aqueous solutions were prepared that contained the alkali
metal picrate (5.0 mM) and the corresponding alkali metal
chloride (55 mM). Into a capped, metal-free, plastic 15-mL
centrifuge tube was placed 1.00 mL of the aqueous metal
picrate solution and 1.00 mL of a 5.0 mM chloroform
solution of the ionophore. The tube was shaken on a vortex
mixer for 5 min for thorough mixing and then centrifuged
for 5 min to promote complete phase separation. A sample
(10 mL) of the aqueous phase was removed with a syringe
and transferred to a 5.0 mL volumetric ¯ask. The ¯ask was
®lled to the mark with MeCN. The absorbance of the
solution at 275 nm was measured with a Shimadzu UV-
260 UV/vis spectrophotometer. The % extraction was
calculated by:
General procedure for the preparation of partially
¯uorinated macrocycles 8 and 15 with penta¯uorobenzyl
groups
To a mixture of the aza macrocycle (5.0 mmol of 22 and
2.5 mmol of 23), 0.69 g (5.0 mmol) of K2CO3 and 20 mL of
MeCN, 1.33 g (5.0 mmol) of penta¯uorobenzyl bromide
was added dropwise over a period of 15 min. The reaction
mixture was stirred at room temperature for 48 h. The
mixture was ®ltered and the ®ltrate was evaporated in
vacuo. The residue was dissolved in CH2Cl2. This solution
was washed with water, dried over Na2SO4 and evaporated
in vacuo to give the crude product.
% Extraction ˆ 100 ꢀAbsbefore 2 Absafter†=Absbefore
N-Penta¯uorobenzyl aza-15-crown-5 (8). The crude
product was puri®ed by column chromatography on silica
gel with CH2Cl2 then EtOAc as eluents to give a yellowish
oil in 60% yield. 1H NMR (CDCl3): d 2.78 (t, 4H, Jˆ6 Hz),
3.63±3.68 (m, 16H), 3.86 (s, 2H). 19F NMR (CDCl3): d
2141.6 to 2141.8 (m, 2F), 2155.6 to 2155.7 (t, 1F),
2162.4 to 2162.6 (m, 2F). Anal. calcd for C17H22F15NO4:
C, 51.13; H, 5.55; N, 3.51. Found: C, 51.40; H, 5.58; N,
3.50.
where Absbefore is the absorbance of a similarly diluted
sample of the unextracted alkali metal picrate solution and
Absafter is the absorbance of the alkali metal picrate soution
after extraction. Three independent extractions were
performed for each combination of alkali metal and iono-
phore. The results were averaged and the standard deviation
was calculated.
N,N0-Bis(Penta¯uorobenzyl) 1,10-diaza-18-crown-6 (15).
Recrystallization from MeOH gave a white solid with mp
Acknowledgements
1
74±758C in 63% yield. H NMR (CDCl3): d 2.78 (t, 8H,
This research was supported by the Texas Higher Education
Coordinating Board-Advanced Technology Program and
the Robert A. Welch Foundation (Grant D-775).
Jˆ6 Hz), 3.60±3.66 (m, 16H), 3.85 (s, 4H). 19F NMR
(CDCl3): d 2141.9 to 2142.0 (m, 4F), 2155.6 to 2155.7
(t, 2F), 2162.5 to 2162.7 (m, 4F). Anal. calcd for
C26H28F10N2O4: C, 50.16; H, 4.53; N, 4.50. Found: C,
49.93; H, 4.50; N, 4.46.
References
General procedure for the preparation of macrocycles
46 and 47
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