Lariat ether carboxylic acids, O-benzylhydroxamates and hydroxamic acids with fluorinated substituents: Synthesis, metal ion complexation and solubility in supercritical carbon dioxide

Article abstract of DOI:10.1016/S0040-4020(00)00380-X

A series of lariat ether carboxylic acids, O-benzylhydroxamates, and hydroxamic acids with fluorine-containing substituents is prepared. In general, the presence of fluorine-containing substituents is found to increase the solubility of the lariat ethers

Full text of DOI:10.1016/S0040-4020(00)00380-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4651±4657
Lariat Ether Carboxylic Acids, O-Benzylhydroxamates and
Hydroxamic Acids with Fluorinated Substituents:
Synthesis, Metal Ion Complexation and Solubility in Supercritical
Carbon Dioxide
Sadik Elshani,a,b Hongshan Du,a Kenneth E. Laintz,a Nicholas R. Natale,a Chien M. Wai,a
Nazar S. A. Elkarimb and Richard A. Bartschb,
*
aDepartment of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
bDepartment of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received 3 February 2000; revised 4 April 2000; accepted 4 May 2000
AbstractÐA series of lariat ether carboxylic acids, O-benzylhydroxamates, and hydroxamic acids with ¯uorine-containing substituents is
prepared. In general, the presence of ¯uorine-containing substituents is found to increase the solubility of the lariat ethers in supercritical
carbon dioxide. Ef®ciencies of the ¯uorine-containing lariat ether carboxylic and hydroxamic acids are compared with those for non-
¯uorinated analogs in solvent extraction of lanthanide ions from aqueous solutions into chloroform. Responses of the ¯uorine-containing
lariat ether O-benzylhydroxamates towards alkali metal cations in solvent polymeric membrane electrodes are compared with those
analogous non-¯uorinated compounds. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
metal, alkaline earth metal, and lanthanide ions.7±20 The
selectivity and pH range for extraction are in¯uenced by
the structure of the ligand.
Lariat ethers are based on crown ethers and have secondary
coordination sites bound to the macrocycle by ¯exible side
arms. Lariat ethers are designed to enhance the cation bind-
ing ability of crown ethers and also partly to mimic the
dynamic complexation processes shown by naturally
occurring macrocyclic ligands.1
Supercritical ¯uid extraction (SFE) of metal species from
solids and liquids has been the subject of several recent
studies.21±28 This technique exhibits high ef®ciency when
a ¯uorinated chelating agent, such as lithium bis(tri¯uoro-
ethyl)dithiocarbamate or a ¯uorinated b-diketone, is used as
an extractant in supercritical carbon dioxide. (This medium is
particularly attractive since it is non-toxic, may be easily
recycled, involves minimal waste generation, gives rapid
separations and its solvation strength is tunable by density
variation.) However, these chelating agents complex with a
variety of metal and non-metal species and are non-selective.
Recently there has been considerable interest in macrocyclic
ligands that contain proton-ionizable functional groups.2
When a proton-ionizable group is incorporated into the
side arm of a lariat ether, the molecule is both a cation
exchanger and a chelator.3 Such an arrangement can provide
an extraction system with greater selectivity and ef®ciency
than one in which an lipophilic organic acid is simply mixed
with a crown ether.3 A very important advantage of these
proton-ionizable lariat ethers is that the ionized group on the
side arm provides the requisite counteranion for transport of
a metal ion into an organic phase during separations by
solvent extraction or transport across liquid membranes.
Dibenzocrown ethers with pendant carboxylic acid4±6 and
hydroxamic acid groups in their side arms6 have been shown
to be ef®cient ligands for the solvent extraction of alkali
In light of the observation that ¯uorinated substituents
increase the solubility of metal chelates in supercritical
carbon dioxide, we were intrigued by the possibility of
introducing ¯uorine-containing substituents into proton-
ionizable lariat ethers. We now report the synthesis of
¯uorine-containing lariat ether carboxylic acids, O-benzyl-
hydroxamates, and hydroxamic acids and the effects of
introducing such substituents on lanthanide ion extraction,
alkali metal cation complexation and solubility in super-
critical carbon dioxide. To the best of our knowledge,
these are ®rst lariat ether carboxylic acids, O-benzylhydrox-
amates, and hydroxamic acids with ¯uorine-containing
substituents.
Keywords: crown ethers; substituent effects; solvents and solvent effects;
complexation.
* Corresponding author. Tel.: 11-806-742-3069; fax: 11-806-742-1289;
e-mail: rabartsch@ttu.edu
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00380-X

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S. Elshani et al. / Tetrahedron 56 (2000) 4651±4657
Scheme 1.
Results and Discussion
isolated as a mixture of regioisomers which could not be
separated by column chromatography.
Synthesis of ¯uorine-containing lariat ethers
The second strategy involved reactions of ¯uorine-contain-
ing aryl Grignard reagents with sym-(keto)dibenzo-16-
crown-5 (4)5 to give lariat ether tertiary alcohols 5±7
(Scheme 2). Reactions of alcohols 6 and 7 with sodium
hydride and bromoacetic acid in THF produced ¯uorine-
containing lariat ether carboxylic acids 8 and 9, respec-
tively. An analogous reaction of sym-(hydroxy)(penta¯uoro-
Two different strategies were employed. In the ®rst,
commercially available 3-¯uorocatechol was used in the
preparation of ring-¯uorinated sym-dibenzo-16-crown-5-
oxyacetic acid 3 (Scheme 1). Thus, 3-¯uorocatechol was
reacted with bis-(2-chloroethyl) ether and sodium hydroxide
in water to produce the ¯uorine-containing bisphenol 1.
Ring closure by reaction of 1 with epichlorohydrin and
sodium hydroxide in water gave lariat ether alcohol 2,
which was reacted with sodium hydride and bromoacetic
acid in THF to produce the ring-¯uorinated lariat ether
carboxylic acid 3. Lariat ether carboxylic acid 3 was
phenyl)-dibenzo-16-crown-5 (5) gave
a complicated
product mixture from which none of the desired lariat
ether carboxylic acid could be isolated. Presumably this
resulted from nucleophilic attack on the penta¯uorophenyl
ring.
Scheme 2.

S. Elshani et al. / Tetrahedron 56 (2000) 4651±4657
4653
Scheme 3.
Solubilities of lariat ether carboxylic acids in super-
critical carbon dioxide
No solubility data for lariat ether carboxylic acids in super-
critical carbon dioxide have appeared in the literature. The
critical temperature (Tc) and pressure (Pc) of carbon dioxide
are 328C and 73 atm, respectively.29 The solubilities of ring-
¯uorinated lariat ether carboxylic acid 3 and the non-¯uori-
nated analog 13 and lariat ether carboxylic acid 9 with a
geminal, ¯uorine-containing substituent in supercritical
carbon dioxide at 508C in the pressure range of 100±
300 atm are given in Table 1.
At pressures of less than 200 atm, 3 exhibits greater solu-
bility in supercritical carbon dioxide than does the non-
¯uorinated analog 13. The solubility difference appears to
depend on the pressure with the greatest difference occur-
ring at 117 atm. Under this condition, the solubility of 3 is
3.8 times higher than that for non-¯uorinated 13. At 200 and
300 atm, there is no difference in the solubilities of 3 and 13.
The solubility of 9 in supercritical carbon dioxide is slightly
higher than that of 3, probably because lariat ether
carboxylic acid 9 contains six ¯uorine atoms instead of
two. However, even for lariat ether carboxylic acid 9, the
solubility in supercritical carbon dioxide is too low for
practical use as a metal ion extractant.
Scheme 4.
Treatment of ¯uorine-containing lariat ether carboxylic
acids 8 and 9 with oxalyl chloride in benzene gave the
corresponding lariat ether acid chlorides which were reacted
with O-benzylhydroxylamine hydrochloride and pyridine in
acetonitrile to form lariat ether O-benzylhydroxamates 10
and 11, respectively (Scheme 2). For 11, catalytic hydro-
genolysis of the O-benzyl group gave ¯uorine-containing
lariat ether hydroxamic acid 12 (Scheme 3).
Solvent extraction of lanthanide ions by lariat ether
carboxylic and hydroxamic acids
The availability of ¯uorine-containing lariat ether
carboxylic acids 3, 8 and 9 and hydroxamic acid 12
encouraged the investigation of their behavior as lanthanide
ion extractants.16,17 Distribution coef®cients for extraction
of La(III) and Lu(III) from aqueous solutions into chloro-
form and the La/Lu selectivities for lariat ether carboxylic
acids 3, 8 and 9 and the des¯uoro analogs 13 and 14 are
given in Table 2. The lariat ether carboxylic acid 3 with a
¯uorine attached to each benzene ring appears to appreci-
ably increase the lanthanide extraction ef®ciency relative to
Non-¯uorinated lariat ether carboxylic acids 134 and 14,6
O-benzylhydroxamates 156 and 16 and hydroxamic acid
176 were prepared by reported or analogous methods for
comparison purposes (Scheme 4).
Structures of the new lariat ether compounds were
consistent with their IR and NMR spectra and veri®ed by
combustion analysis.
Table 1. Solubilities of lariat ether carboxylic acids in supercritical carbon dioxide at 508C as a function of pressure. The estimated error is ^20% of the stated
value
Lariat ether
Pressure (atm)
150
100
117
200
300
3
13
9
7:9 £ 1026
7:6 £ 1026
3:0 £ 1025
M
M
M
8:4 £ 1025
2:2 £ 1025
9:0 £ 1025
M
M
M
9:9 £ 1025
1:3 £ 1024
M
1:2 £ 1024
1:2 £ 1024
1:6 £ 1024
M
M
M
2:1 £ 1024
2:1 £ 1024
2:1 £ 1024
M
M
M
7:6 £ 1025 M
M

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S. Elshani et al. / Tetrahedron 56 (2000) 4651±4657
Table 2. Distribution coef®cients for the solvent extraction of lantha-
num(III) and lutetium(III) from aqueous solutions at pH 6.5^0.2 into
chloroform by ¯uorine-containing lariat crown ether carboxylic acids 3, 8
and 9 and hydroxamic acid 12. The estimated error is ^10% of the stated
value. Values for non-¯uorinated lariat ether carboxylic acids 13 and 14 and
hydroxamic acid 17 are shown for comparison
systematically varied from phenyl to 3-methylphenyl to
3-(tri¯uoromethyl)phenyl to 3,5-di(tri¯uoromethyl)phenyl
in ligands 15, 16, 10 and 11, respectively.
For all four ion-selective electrodes, the greatest potentio-
metric response is for Na1 which provides the best ®t for a
dibenzo-16-crown-5 cavity.31,32 The Na1/Li1 selectivities
are very high and remain approximately the same when
one or two tri¯uoromethyl groups are introduced into the
geminal aryl group. On the other hand, the Na1/K1 selec-
tivity is much lower and exhibits a perceptible decrease as
the number of tri¯uoromethyl groups is enhanced. A
diminution of Na1 selectivity with the introduction of
tri¯uoromethyl groups is clearly evident when the com-
peting alkali metal cations are Rb1 and Cs1. Although
Na1 ®ts within the crown ether cavity to form a nesting
complex,33 K1, Rb1 and Cs1 are too large and form perch-
ing complexes.33 Apparently the addition of tri¯uoromethyl
groups to the geminal aryl group lessens the disfavoring for
formation of a perching complex versus a nesting complex
with an alkali metal cation.
Lariat ether
DLu31
DLa31
Ratio (Lu31/La31
)
3
13
8
39
13.3
3.0
2.9
6.5
19.6
4.82
2.99
7.96
75.9
147
0.25
0.22
0.35
1.27
0.25
19.2
13.6
23.1
59.8
588
9
14
12
17
non-¯uorinated analog 13, even though the La/Lu selectiv-
ity is decreased. For ¯uorine-containing lariat ether
carboxylic acids 8 and 9 and the non-¯uorinated analog
14, the lanthanide extraction ef®ciency and the La/Lu selec-
tivity decrease as the geminal substituent is varied C6H5.3-
(CF3)C6H4.3,5-(CF3)2C6H3.
Compared with lariat ether carboxylic acid 9, the analogous
lariat ether hydroxamic acid 12 exhibits a 25-fold increase
in Lu(III) extraction, but only a six-fold increase in La(III)
extraction. Thus, the lariat ether hydroxamic acid 12
exhibits a much higher Lu/La selectivity than does the
analogous carboxylic acid. When the geminal 3,5-di(tri-
¯uoromethyl)phenyl group in lariat ether hydroxamic acid
12 is replaced by a phenyl group in 17, the extraction
ef®ciency for Lu(III) increases by approximately two-fold,
but the extraction of La(III) drops by a factor of ®ve. For all
of the proton-ionizable lariat ethers examined in this study,
the Lu/La selectivity is greatest for the non¯uorinated lariat
ether hydroxamic acid 17.
Experimental
Materials and methods
The 3-¯uorocatechol was obtained from Aldrich and used
without puri®cation. Other ¯uorinated compounds were
purchased from PCR. Tetrahydrofuran was distilled from
benzophenone ketyl. sym-(Keto)dibenzo-16-crown-55 and
non-¯uorinated lariat ethers 13±15 and 17 were prepared
by reported methods.4,6 NMR spectra were obtained with a
Bruker AF200 spectrometer (200 MHz for 1H and
188.31 MHz for 19F). Combustion analyses were performed
by Desert Analytics Laboratory, Tucson, AZ.
Potentiometric selectivities of lariat ether O-benzyl-
hydroxamates for alkali metal cations in solvent
polymeric membrane electrodes
Synthesis of bis-2-[3(4)-¯uoro-2-hydroxyphenoxy]ethyl
ether (1). To a solution of 3-¯uorocatechol (20.0 g,
156 mmol) in 200 mL of water under nitrogen, NaOH
(2.14 g, 53.64 mmol) was added and the reaction mixture
was warmed to re¯ux. Bis(2-chloroethyl) ether (2.78 mL,
26.2 mmol) was added slowly over a 3 h period and re¯ux-
ing was continued for 48 h. Upon cooling to room tempera-
ture, a dark oil separated which solidi®ed on standing. This
solid was recrystallized from benzene±petroleum ether to
give 1.80 g (21%) of 1 as a white solid with mp 67±688C: IR
(KBr) 3406 (OH) cm21; 1H NMR (CDCl3) d 3.77±4.25 (m,
8H), 6.61±6.94 (m, 6H), 7.55 (s, 2H); 19F NMR (CDCl3) d
2131.5 (m, 1F), 2136.0 (m, 1F). Anal. calcd for
C16H16F2O5: C: 58.89; H, 4.94. Found: C, 58.79; H, 4.94.
Metal-ion selectivities of non-ionizable macrocyclic ligands
are frequently determined with polymeric membrane
electrodes.30 (Due to their ion-exchange behavior, proton-
ionizable macrocyclic ligands are not suitable.) To probe the
in¯uence of introducing one and two tri¯uoromethyl groups
into the geminal aryl group of O-benzyl sym-(aryl)dibenzo-
16-crown-5-oxyacetylhydroxamates, plasticized poly-
(vinyl chloride) membranes containing lariat ethers 10, 11,
15 and 16 were prepared and incorporated into ion-selective
electrode assemblies and their potentiometric selectivities
were measured (Table 3). The geminal aryl group is
Pot
Table 3. Potentiometric selectivities, 2log K
Na,M
dibenzo-16-crown-5-oxyacetyl-hydroxamates. The standard deviation of
the log KPot values from the average obtained from duplicate determinations
with two membranes was less than 0.05
sym-(Hydroxy)-3(6),30 (60)-di¯uorodibenzo-16-crown-5
(2). A mixture of bisphenol 1 (1.68 g, 5.15 mmol), NaOH
(0.41 g, 10.3 mmol) and water (120 mL) was stirred under
nitrogen at 908C until a solution was obtained. The solution
was cooled to 508C and epichlorohydrin (0.48 g,
5.15 mmol) was added over a 3-h period. The reaction
mixture was stirred for an additional 5 h and then cooled
to room temperature. The aqueous solution was decanted
from the oily residue, which was dissolved in CH2Cl2.
The resultant solution was washed with water, dried
over MgSO4 and evaporated in vacuo. The residue was
, of O-benzyl sym-(aryl)-
Pot
Na,M
Lariat ether
Aryl group
2log K
for M1
Rb1
Li1
K1
Cs1
15
16
10
11
C6H5
3.42
3.55
3.40
3.39
1.60
1.56
1.52
1.44
2.04
2.10
1.77
1.56
2.34
2.36
1.79
1.19
3-(CH3)C6H4
3-(CF3)C6H4
3,5-(CF3)C5H3

S. Elshani et al. / Tetrahedron 56 (2000) 4651±4657
4655
recrystallized from petroleum ether to give 0.65 g (33%) of
2 as a white solid with mp 78±808C: IR (KBr) 3441(OH),
1256, 1124 (C±O) cm21; 1H NMR (CDCl3) d 3.46 (s, 1H),
3.76±4.47 (m, 13H), 6.65±7.16 (m, 6H); 19F NMR (CDCl3)
d 2130.9 (m, 1F), 2131.8 (m, 1F). Anal. calcd for
C19H20F2O6: C, 59.68; H, 5.27. Found: C, 59.91; H, 5.48.
dissolved in THF (15 mL) was added over a 30-min period.
Stirring was continued for 1 h and a solution of bromoacetic
acid (0.56 g, 4.0 mmol) in THF (15 mL) was added over a
3-h period. After stirring for an additional 15 h, water was
added cautiously to destroy the excess NaH. The THF was
evaporated in vacuo from the mixture and the aqueous
mixture was extracted with Et2O (to remove the unreacted
lariat ether alcohol), acidi®ed with 6 N HCl and extracted
with CH2Cl2. The combined organic layers were washed
with water, dried over Na2SO4 and evaporated in vacuo.
General method for the preparation of lariat ether
alcohols 5±7
A three-necked ¯ask was charged with 0.144 g (6.0 mmol)
of magnesium turnings and ¯ame-dried under an
atmosphere of dry nitrogen. THF (20 mL) and a crystal of
iodine were added. A small portion of the substituted
bromobenzene was added to initiate the reaction. The reac-
tion mixture was cooled with an ice bath to control the
reaction once it commenced. After the initial reaction
subsided, the remainder of the substituted bromobenzene
was added slowly. After completion of the addition, the
reaction mixture was stirred for 1 h and a solution of
1.03 g (3.0 mmol) of sym-(keto)dibenzo-16-crown-5 in
10 mL of THF was added dropwise. Stirring at room
temperature was continued overnight and then 20 mL of
5% aqueous NH4Cl solution was added. The mixture was
stirred for 10 h and the THF was evaporated in vacuo. The
residue was extracted with CH2Cl2 and the CH2Cl2 layer
was washed with water, dried over MgSO4 and evaporated
in vacuo. The residue was chromatographed on silica gel
with CH2Cl2 and then Et2O as eluents to afford the product.
sym-3(6),30(60)Di¯uorodibenzo-16-crown-5-oxyacetic acid
(3). It was obtained in 49% yield as a white solid after
trituration with Et2O, mp 129±1318C: IR (KBr) 3437
(COOH), 1732 (CvO), 1255, 1124 (C±O) cm21 1H
;
NMR (CDCl3) d 3.85±4.51 (m, 15H), 6.67±6.99 (m, 6H);
19F NMR (CDCl3) d 2129.9 (m, 1F), 2131.3 (m, 1F). Anal.
calcd for C21H22F2O8: C, 57.27; H, 5.03; F, 8.62. Found: C,
57.24; H, 4.96; F, 8.32.
sym-[3-(Tri¯uoromethyl)phenyl]dibenzo-16-crown-5-
oxyacetic acid (8). It was obtained in 89% yield as a white
solid with mp 126±1288C: IR (KBr) 3410 (COOH), 1724
1
(CvO), 1256, 1124 (C±O) cm21; H NMR (CDCl3) d
3.73±4.18 (m, 8H), 4.36 (d, Jˆ10.6, 2H), 4.74 (d,
Jˆ10.6 Hz, 2H), 4.90 (s, 2H), 6.68±6.98 (m, 8H), 7.58±
7.63 (m, 2H), 7.87±7.94 (m, 2H); 19F NMR (CDCl3) d
262.5 (s). Anal. calcd for C28H27F3O8: C, 61.30; H, 4.93;
F, 10.39. Found: C, 61.04; H, 5.17; F, 10.25.
sym-[3,5-Di(tri¯uoromethyl)phenyl]dibenzo-16-crown-
5-oxyacetic acid (9) It was obtained in 96% yield after
puri®cation by chromatography on silica gel with
CH2Cl2±MeOH (9:1) as eluent as a white solid with mp
128±1308C: IR (KBr) 3421 (COOH), 1735 (CvO), 1257,
1132 (C±O) cm21; 1H NMR (CDCl3) d 3.70±4.17 (m, 8H),
4.45 (d, Jˆ10.68 Hz, 2H), 4.71 (d, Jˆ10.68 Hz, 2H), 4.89
(s, 2H), 6.70±6.99 (m, 8H), 7.89 (s, 1H), 8.19 (s, 2H); 19F
NMR (CDCl3) d 263.7 (s). Anal. calcd for C29H26F6O8: C,
56.49; H, 4.25; F, 18.49. Found: C, 56.14; H, 4.36; F, 18.13.
sym-(Hydroxy)(penta¯uorophenyl)dibenzo-16-crown-5
(5). It was obtained in 48% yield as a white solid with mp
128±1298C: IR (KBr) 3339 (OH), 1258, 1123 (C±O) cm21
;
1H NMR (CDCl3) d 3.91±4.26 (m, 8H), 4.52 (d, Jˆ9.6 Hz,
2H), 4.62 (d, Jˆ9.6 Hz, 2H), 6.79±7.00 (m, 8H); 19F NMR
(CDCl3) d 2138 (s, 2F), 2155 (s, 1F), 2162 (s, 2F). Anal.
calcd for C25H21F5O6: C, 58.60; H, 4.13. Found: C, 58.20; H,
4.32.
sym-(Hydroxy)[3-(tri¯uoromethyl)phenyl]dibenzo-16-
crown-5 (6). It was obtained in 75% yield as a white solid
with mp 54±568C: IR (KBr) 3444 (OH), 1258, 1122 (C±O)
cm21; 1H NMR (CDCl3) d 3.45 (s, 1H), 3.83±4.20 (m, 8H),
4.36 (d, Jˆ9.5 Hz, 2H), 4.50 (d, Jˆ9.52 Hz, 2H), 6.78±6.96
(m, 8H), 7.45±7.57 (m, 2H), 7.96±8.07 (m, 2H); 19F NMR
(CDCl3) d 262.4 (s). Anal. calcd for C26H25F3O6: C, 63.67;
H, 5.14. Found: C, 64.07; H, 5.15.
General procedure for the synthesis of O-benzyl sym-
(aryl)dibenzo-16-crown-5-oxyacetylhydroxamates 10
and 11
To a solution of the appropriate lariat ether carboxylic acid
(3.0 mmol) in benzene (20 mL) at 08C was added dropwise
oxalyl chloride (1.05 mL, 12.0 mmol). The mixture was
stirred at room temperature for 1 h and then heated at
708C for 1 h. The mixture was cooled to room temperature
and evaporated in vacuo to provide a residue of the lariat
ether acid chloride which was used directly in the next step.
The residue was dissolved in MeCN and added dropwise to
a solution mixture of O-benzylhydroxylamine hydro-
chloride (0.48 g, 3.0 mmol) and pyridine (0.48 g,
6.0 mmol) in MeCN at 08C under nitrogen. The mixture
was stirred for 24 h. The solvent was evaporated in vacuo
and the residue was dissolved in EtOAc. The solution was
washed with 0.6 N HCl, water and 0.6 M aqueous sodium
bicarbonate, dried over Na2SO4 and evaporated in vacuo.
sym-(Hydroxy)[3,5-bis(tri¯uoromethyl)phenyl]dibenzo-
16-crown-5 (7). It was obtained in 68% yield as a white
solid with mp 56±588C: IR (KBr) 3441 (OH), 1259, 1135
(C±O) cm21; 1H NMR (CDCl3) d 3.82±4.20 (m, 8H), 4.29
(d, Jˆ9.57 Hz, 2H), 4.64 (d, Jˆ9.55 Hz, 2H), 6.79±6.98 (m,
8H), 7.80 (s, 1H), 8.32 (s, 2H); 19F NMR (CDCl3) d 262.5
(s). Anal. calcd for C27H24F6O6: C, 58.07; H, 4.33. Found: C,
57.89; H, 4.59.
General method for the synthesis of lariat ether
carboxylic acids 3, 8 and 9
A 100 mL three-necked ¯ask was charged with NaH
(0.34 g, 14 mmol) and THF (20 mL) under nitrogen and a
solution of the appropriate lariat ether alcohol (2.0 mmol)
O-benzyl sym-[3-(tri¯uoromethyl)phenyl]dibenzo-16-
crown-5-oxyacetylhydroxamate (10). It was realized in

4656
S. Elshani et al. / Tetrahedron 56 (2000) 4651±4657
46% yield as a white solid with mp 63±658C after puri®ca-
tion by column chromatography on silica gel with CH2Cl2
then CH2Cl2±EtOAc (9:1) as eluents followed by recrystal-
lization from EtOAc±hexanes: IR (deposit from CH2Cl2
solution on a NaCl plate) 3281 (NH), 1686 (CvO), 1257,
1124 (C±O) cm21; 1H NMR (CDCl3) d 3.86±3.91 (m, 2H),
4.01±4.17 (m, 6H), 4.31 (d, 2H, Jˆ10.6 Hz), 4.68 (d, 2H,
Jˆ10.6 Hz), 4.83 (s, 2H), 4.91 (s, 2H), 6.68±6.99 (m, 8H),
7.22±7.32 (m, 5H), 7.35±7.73 (m, 3H), 7.86 (s, 1H), 9.43 (s,
1H). Anal. calcd for C35H34F3NO8: C, 64.31; H, 5.24; N,
2,14. Found; C, 64.32; H, 5.26; N, 2.01.
1.0£1024 M aqueous solution (10 mL) of the lanthanide
nitrate containing a rare-earth radioisotope as a tracer with
a Burrell Model 75 mechanical shaker for 30 min at room
temperature. After the separation of the phases, 5.0 mL
portions of each phase were removed and subjected to g
counting.34
Potentiometric responses of solvent polymeric mem-
brane electrodes to alkali metal cations
Membranes containing poly(vinyl choride), o-nitrophenyl
octyl ether (the membrane solvent), potassium tetrakis(p-
chlorophenyl)borate and the lariat ether were prepared by
the reported method.31,32 Potentiometric measurements
were performed as before and selectivity coef®cients
(KPot) were determined by the ®xed interference method.35
O-benzyl sym-[3,5-di(tri¯uoromethyl)phenyl]dibenzo-
16-crown-5-oxyacetylhydroxamate (11). It was obtained
in 83% yield as a white solid with mp 59±618C: IR (KBr)
1
3290 (NH), 1689 (CvO), 1258, 1135 (C±O) cm21; H
NMR (CDCl3) d 3.84±4.15 (m, 8H), 4.37 (d, Jˆ10.7 Hz,
2H), 4.62 (d, Jˆ10.7 Hz, 2H), 4.80 (s, 2H), 4.89 (s, 2H),
6.67±6.98 (m, 8H), 7.17±7.29 (m, 5H), 7.87 (s, 1H), 8.07 (s,
2H), 9.40 (s, 1H); 19F NMR (CDCl3) d 262.8 (s). Anal.
calcd for C36H33F6NO8: C, 59.92; H, 4.61, N, 1.94. Found:
C, 59.96; H, 4.56; N, 2.01.
Acknowledgements
The research conducted at the University of Idaho was
supported by the National Science Foundation's EPSCoR
Program, Grant #R11-8902065. The research performed at
Texas Tech University was supported by the Division of
Chemical Sciences of the Of®ce of Basic Energy Sciences
of the US Department of Energy, Grant DE-FG03-
94ER14416.
Preparation of sym-[3,5-di(tri¯uoromethyl)phenyl]di-
benzo-16-crown-5-oxy-acetylhydroxamic acid (12). The
O-benzyl hydroxamate ester 11 (1.54 g, 2.14 mmol) was
dissolved in MeOH (120 mL) and 0.2 g of 10% Pd on
charcoal was added. The mixture was stirred under one
atmosphere of hydrogen at room temperature for 3 h and
®ltered. The ®ltrate was evaporated in vacuo to give a
97% yield of 12 as a white solid with mp 85±78C: IR
(KBr) 3387 (NHOH), 1678 (CvO), 1259, 1136 (C±O)
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