Neutral Anion Receptors: Synthesis and Evaluation as Sensing Molecules in Chemically Modified Field Effect Transistors

Article abstract of DOI:10.1021/jo9707040

A new class of anion selective receptors is based on the neutral uranylsalophene building block as Lewis acidic binding site. Additional hydrogen bond accepting or donating moieties near the anion binding site offer the possibility of varying the binding

Full text of DOI:10.1021/jo9707040

9034
J . Org. Chem. 1997, 62, 9034-9038
Neu tr a l An ion Recep tor s: Syn th esis a n d Eva lu a tion a s Sen sin g
Molecu les in Ch em ica lly Mod ified F ield Effect Tr a n sistor s
Martijn M. G. Antonisse, Bianca H. M. Snellink-Rue¨l, Isteyfo Yigit,
J ohan F. J . Engbersen, and David N. Reinhoudt*
Department of Supramolecular Chemistry and Technology, MESA Research Institute, University of
Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
Received April 21, 1997X
A new class of anion selective receptors is based on the neutral uranylsalophene building block as
Lewis acidic binding site. Additional hydrogen bond accepting or donating moieties near the anion
binding site offer the possibility of varying the binding selectivity. Field effect transistors chemically
modified with such receptors exhibit anion selectivities that strongly deviate from the classical
Hofmeister series favoring phosphate or fluoride anions, depending on the structure of the
uranylsalophenes. The phosphate selective chemically modified field effect transistors (CHEMFETs)
detect phosphate with high selectivity over much more lipophilic anions, such as nitrate (log
Pot
H2PO4,NO3
K
) -1.3), at [H2PO4-] g 6.3 × 10-4 M. CHEMFETs modified with salophenes with amido
substituents result in a high fluoride selectivity; even in the presence of 0.1 M chloride, fluoride
can be detected at [F-] g 6 × 10-4 M (log K
Pot
) -2.0).
F,Cl
In tr od u ction
be further influenced by functionalization of the uranyl-
salophene with additional binding sites that can form
hydrogen bonds. Recently these receptors have been
used successfully in combination with cation receptor
molecules to selectively transport salts through supported
liquid membranes.8
This paper describes the synthesis of a second genera-
tion of uranylsalophene derivatives which show high
selectivity for phosphate and fluoride, together with their
application as sensing molecules in membrane sensors.
These novel uranylsalophenes all have dodecyl chains in
order to increase the lipophilicity, and in addition they
have hydrogen bond accepting methoxy or hydrogen bond
donating acetamido groups in close proximity to the anion
coordination site. The additional binding sites tune the
selectivity with respect to individual anions.
Compared with synthetic neutral receptors for cations,
such receptors for anions have only recently received the
attention they deserve. Both in membrane transport1
and anion sensing,2 such receptors will be required in
order to obtain sufficient selectivity. The wide variety
of analytes in waste water, e.g. nitrate, phosphate, and
halides, or in clinical chemistry, e.g. chloride and sali-
cylate, stimulate our work on highly selective sensors.
Sensors for lipophilic anions, like nitrate, can be obtained
with ion-exchange membranes that introduce a selectiv-
ity following the relative dehydration energies of the
anions (i.e. the so-called Hofmeister series).3 Most sen-
sors described in the literature for the detection of
hydrophilic ions contain organotin derivatives4 or met-
alloporphyrins5 as the receptor in the ion-selective mem-
brane to selectively bind the target anion. A drawback
of the organotin receptors is their limited stability, and
furthermore with both types of receptors, tuning of the
selectivity by introducing additional binding sites is
difficult.6
Resu lts a n d Discu ssion
Syn th esis. The salophenes were prepared by conden-
sation of 1,2-phenylenediamine 3 with 2 equiv of the
appropriate salicylaldehyde derivative. To increase the
lipophilicity of the salophene derivatives, the 1,2-phen-
ylenediamine moiety was substituted with two dodecyl
ether groups. Alkylated catechol 1 gave, after nitration,
1,2-dinitro-4,5-bis(dodecyloxy)benzene (2) that was re-
duced to the diamine 3 in an overall yield of 60% (Scheme
1).
Previously, we have reported a number of uranyl-
salophene derivatives which show selective binding of
anions in organic solvents.7 In these neutral receptors
four of the five equatorial coordination sites of the uranyl
cation are occupied by the salophene, and the fifth site
is available for anion binding. The binding of anions can
Diamine 3 was used to synthesize the lipophilic ura-
nylsalophene derivatives 7, 8, 9, and 13. The parent
salophene 7 and the methoxy-substituted salophenes 8
and 9 were prepared in 45-50% yield by reaction of 3
with 2 equiv of the appropriate salicylaldehyde (respec-
tively 4, 5, and 6) and 1 equiv of UO2(OAc)2‚2H2O in
methanol (Scheme 2).
X Abstract published in Advance ACS Abstracts, December 1, 1997.
(1) Visser, H. C.; Reinhoudt, D. N.; de J ong, F. Chem. Soc. Rev. 1994,
75-81.
(2) (a) Diamond, D.; McKervey, M. A. Chem. Soc. Rev. 1996, 15-
24. (b) Reinhoudt, D. N. Recl. Trav. Chim. Pays-Bas 1996, 115, 109-
118.
(3) Wegman, D.; Weiss, H.; Ammann, D.; Morf, W. E.; Pretsch, E.;
Sugahara, K.; Simon, W. Microchim. Acta 1984, 3, 1-16.
(4) (a) Wuthier, U.; Pham, H. V.; Zu¨nd, R. Welti, D.; Funck, R. J .
J .; Bezegh, A.; Ammann, D.; Pretsch, E.; Simon, W. Anal. Chem. 1984,
56, 535-538. (b) Tsagatakis, J . K.; Chaniotakis, N. A.; J urkschat, K.
Helv. Chim. Acta 1994, 77, 2191-2196.
(5) (a) Malinowska, E.; Meyerhoff, M. E. Anal. Chim. Acta 1995,
300, 33-43. (b) Gao, D.; Li, J .-Z.; Yu, R.-Q.; Zheng, G.-D. Anal. Chem.
1994, 66, 2245-2249. (c) Chaniotakis, N. A.; Park, S. B.; Meyerhoff,
M. E. Anal. Chem. 1989, 61, 566-570.
(6) Some effect on the selectivity of porphyrins was obtained by the
introduction of bulky substituents that introduce size selectivity. See:
Chaniotakis, N. A.; Chasser, A. M.; Meyerhoff, M. E.; Groves, J . T.
Anal. Chem. 1988, 60, 188-191.
(7) Rudkevich, D. M.; Verboom, W.; Brzozka, Z.; Palys, M. J .;
Stauthamer, W. P. R. V.; van Hummel, G. J .; Franken, S. M.; Harkema,
S.; Engbersen, J . F. J .; Reinhoudt, D. N. J . Am. Chem. Soc. 1994, 116,
4341-4351.
(8) (a) Rudkevich, D. M.; Brzozka, Z.; Palys, M.; Visser, H. C.;
Verboom, W.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1994,
33, 467-468. (b) Visser, H. C.; Rudkevich, D. M.; Verboom, W.; De
J ong, F.; Reinhoudt, D. N. J . Am. Chem. Soc. 1994, 116, 11554-
111555. (c) Rudkevich, D. M.; Mercer-Chalmers, J . D.; Verboom, W.;
Ungaro, R.; De J ong, F.; Reinhoudt, D. N. J . Am. Chem. Soc. 1995,
117, 6124-6125.
S0022-3263(97)00704-4 CCC: $14.00 © 1997 American Chemical Society

Neutral Anion Receptors
Sch em e 1
J . Org. Chem., Vol. 62, No. 26, 1997 9035
Sch em e 2
F igu r e 1. Phosphate response of CHEMFET with receptor 7
in the presence of 0.1 M NaCl (in 0.01 M MES, pH 4.5).
Ta ble 1. Sen sor Ch a r a cter istics of P h osp h a te Selective
CHEMF ETs w ith Recep tor s 7-9
log KPHot
-
(slope mV/decade)
Cl-
SO4
b
2PO4j
recep- detection
tor
limita
NO3
Br-
2-
7
8
9
-3.2 [-56] -1.3 [-50] -1.7 [-52] -1.8 [-53] -2.3 [-53]
-3.8 [-50] -0.7 [-40]c -2.0 [-30] -2.3 [-37] -3.3 [-39]
-3.1 [-56] -0.2 [-42]c -1.2 [-57] -1.6 [-54] -2.3 [-53]
a
b
0.01 M MES, pH ) 4.5. [j] ) 0.1 M in 0.01 M MES, pH )
4.5. c [NO3-] ) 0.01 M in 0.01 M MES, pH ) 4.5.
Sch em e 3
uranyl center. The incorporation of receptor 7 in the
membrane renders the sensor sensitive and selective for
the hydrophilic monovalent dihydrogen phosphate anion.
Figure 1 shows that even in the presence of a large excess
of chloride (0.1 M) the sensor starts responding to the
dihydrogen phosphate ions at concentrations g6 × 10-4
M with a close to Nernstian response of -53 mV/decade
at concentrations g3.2 × 10-3 M. This sensor is selective
for dihydrogen phosphate over many other and much
more lipophilic anions (Table 1). Even in the presence
of the lipophilic nitrate anion, the sensor is 20 times more
Pot
H2PO4,NO3
sensitive for phosphate (log K
) -1.3). This
remarkable selectivity deviates strongly from the Hofmeis-
ter selectivity commonly observed with ion-exchange
membrane sensors.3 Such ion-exchange membrane sen-
sors have usually a 103-104 higher selectivity for nitrate
over phosphate, indicating that the sensor with receptor
7 increases the phosphate selectivity with a factor of 2
× 104 to 2 × 105.
The acetamido-substituted salophene 13 was obtained
under similar conditions in 30% yield, starting from
salicyl aldehyde derivative 12. Compound 12 was ob-
tained by reaction of 4-tert-butyl-2-aminophenol (10) with
acetic acid anhydride, followed by formylation with
hexamethylenetetraamine (HMTA) in trifluoroacetic acid
(Scheme 3).
An ion Selectivity. The anion selectivity of the ura-
nylsalophenes was evaluated by the application of these
receptors as the sensing molecule in potentiometric anion
sensors, in anology with the experiments previously
reported for calix[4]arene-based cation receptors.9 Plas-
ticized PVC membranes (plasticized with 65 wt % of
o-nitrophenyl n-octyl ether (o-NPOE), and containing 1
wt % of uranylsalophene receptor and 20 mol % tetraoc-
tylammonium bromide with respect to the receptor) were
cast on chemically modified field effect transistors (CHEM-
FETs).10
When the o-methoxy-substituted salophene derivative
8 was incorporated in the sensing membrane, a distinct
change in the sensor characteristics was observed (Table
1). The detection limit for phosphate is further lowered
to 1.6 × 10-4 M, and also the selectivity in the presence
of halides and sulfate is further enhanced by a factor of
Pot
H2PO4,Cl
3-10 (log K
) -1.8 and -2.3 respectively for 7
Pot
and 8, and log K
) -2.3 and -3.3).11 The
H2PO4,SO4
favorable effect on the phosphate sensitivity, reflected in
the improved detection limit, is most likely due to
additional hydrogen bond formation of a dihydrogen
phosphate anion coordinated to the Lewis acidic uranyl
center, with the hydrogen bond accepting methoxy groups
of the receptor. Previously we have reported X-ray
crystal structures that indeed show that hydrogen bonds
The anion-binding selectivity of the parent salophene
7 is governed by the character of the electron-accepting
(10) Chemically Modified Field Effect Transistors (CHEMFETs) are
silicon-based microsensors that can transduce the membrane potential
of an ion selective membrane deposited on top of the semiconductor
into an electronic signal. See also ref 16.
(11) The sensors with receptor 8 show a lowered upper detection
limit compared with 7 and 9. This results in a sigmoid shape of the
response curve and consequently in a reduced slope.
(9) (a) Cobben, P. L. H. M.; Egberink, R. J . M.; Bomer, J . G.;
Bergveld, P.; Verboom, W.; Reinhoudt, D. N. J . Am. Chem. Soc. 1992,
114, 10573-10582. (b) Casnati, A.; Pochini, A.; Ungaro, R.; Bocchi,
C.; Ugozzoli, F.; Egberink, R. J . M.; Struijk, H.; Lugtenberg, R. J . W.;
de J ong, F.; Reinhoudt, D. N. Chem. Eur. J . 1996, 2, 436-445.

9036 J . Org. Chem., Vol. 62, No. 26, 1997
Antonisse et al.
Ta ble 2. Sen sor Ch a r a cter istics of F lu or id e Selective CHEMF ETs w ith Recep tor s 7, 8, a n d 13
Pot
F,j
b
log K
(slope mV/decade)
Br-
detection
limita
receptor
ClO4
>0
>0
-1.7 [-37]
NO3
Cl-
SO4
-
-
2-
7
8
13
-2.9 [-44]
-3.0 [-48]
-3.2 [-53]
-0.7 [-41]c
-0.5 [-41]c
-2.0 [-49]
-1.1 [-38]
-1.6 [-47]
-2.1 [-50]
-1.3 [-46]
-1.9 [-49]
-2.0 [-50]
-2.3 [-39]
-2.2 [-50]
-2.5 [-50]
a
b
0.01 M MES, pH ) 6.0. [j] ) 0.1 M in 0.01 M MES, pH ) 6.0. c [NO3-] ) 0.01 M in 0.01 M MES, pH ) 6.0.
are formed between dihydrogen phosphate bound to an
o-methoxy-substituted uranylsalophene and adjacent
methoxy groups.7 An additional effect of the presence of
the methoxy substituents near the uranyl binding center
will be the reduction of the size of the binding cleft and
the increased electrostatic repulsion with the relatively
large interfering halide ions. The presence of the electron-
donating methoxy substituents furthermore reduces the
electrophilicity of the uranyl center, thereby affecting its
anion binding strength.7 This electronic effect causes the
reduced selectivity of the “hard” phosphate over the
“softer” nitrate anion of receptor 8 as reflected in CHEM-
FETs with the p-methoxyuranylsalophene derivative 9.
The methoxy groups of 9 should have approximately the
same effect on the charge density of the uranyl center as
in 8, but cannot form additional hydrogen bonds with
F igu r e 2. Fluoride response of CHEMFET with receptor 13
in the presence of 0.1 M NaClO4 (in 0.01 M MES, pH 6.0).
halides, nitrate, and sulfate (Table 2). As is shown in
Figure 2 even in the presence of a large excess of the very
phosphate. This results in a reduced phosphate over
Pot
H2PO4,NO3
nitrate selectivity (log K
) -0.2 with receptor 9
lipophilic perchlorate ion (0.1 M) it is possible to deter-
vs -1.3 with receptor 7, Table 1). Compared with
receptor 9 the phosphate over nitrate selectivity of
receptor 8 is increased due to the additional hydrogen
bond formation of phosphate.
Pot
F,ClO4
mine fluoride at the (sub)millimolar level (log K
)
-1.7). This implies an enhancement of the fluoride
selectivity over perchlorate of at least 106 when compared
with the Hofmeister selectivity observed in ion-exchange
membrane sensors.
As the uranyl center strongly binds low polarizable
(hard) anions of high electron density, the receptors were
also evaluated for their fluoride selectivity. Besides
having a high electron density, fluoride is also a strong
hydrogen bond acceptor, and this makes this ion very
hydrophilic and difficult to extract into organic media.
Selective measurement of fluoride anions with polymeric
membrane sensors therefore requires the presence of
extremely selective fluoride receptors in the membrane.
Incorporation of the parent salophene 7 in the sensor
membrane introduces fluoride sensitivity with a detection
limit of [F-] ) 1.3 × 10-3 M. The selectivity for fluoride
with respect to the more lipophilic halide ions is g10,
but nitrate ions significantly interfere when present at
equal or higher concentrations (Table 2). The selectivity
of the receptor for fluoride could be improved by optimi-
zation of the binding cleft for the specific characteristics
of this ion. The data for salophene 8 in Table 2 show
that already the reduction of the binding cleft by the
presence of the o-methoxy substituents results in im-
In summary, we have developed a new generation of
lipophilic uranylsalophene derivatives that can be applied
as selective receptors in anion sensitive membrane sen-
sors. It is very important that the anion selectivity can
favorably be tuned by the introduction of additional
binding sites close to the anion binding site of the neutral
uranyl salophene binding site. Incorporation of these
novel ion receptors in polymeric membranes on chemi-
cally modified field effect transistors enables the evalu-
ation of their anion binding properties and the determi-
nation of the ion activity of the very hydrophilic
dihydrogen phosphate and fluoride anions in aqueous
solutions, even in the presence of an excess of very
lipophilic ions such as nitrate and perchlorate.
Exp er im en ta l Section
Gen er a l. NMR spectra were recorded in CDCl3 unless
stated otherwise, with TMS as internal standard at 250 MHz.
Ion fast atom bombardment (FAB) mass spectra were obtained
with m-nitrobenzyl alcohol as a matrix. Melting points are
uncorrected. CH2Cl2 was distilled from CaCl2 and stored over
molecular sieves (4 Å). All commercially available chemicals
were of reagent grade quality from Acros, Aldrich, or Merck
and were used without further purification. 1,2-Bis(dodecyl-
oxy)benzene (1) was made according to a literature procedure.12
Ca u tion : Care should be taken when handling uranyl-
containing compounds because of their toxicity and radioactiv-
ity.13
1,2-Bis(d od ecyloxy)-4,5-d in itr oben zen e (2). To a cooled
(15 °C) mixture of 4.5 g (0.01 mol) of 1 and 70 mL of glacial
acetic acid in 70 mL of dichloromethane was slowly added 10
mL of concentrated nitric acid (65%), while keeping the
temperature below 40 °C. After being stirred for 30 min, the
proved selectivity for fluoride over the larger chloride and
Pot
F,Cl
bromide ions (e.g. log K
) -1.3 and -1.9 respectively
for salophene 7 and 8). The fluoride sensitivity, reflected
in the detection limit and slope of the response curve of
the sensor, is also slightly improved compared with 7 as
the receptor. However, excellent fluoride sensitivity and
selectivity was obtained only with sensors that contain
the anion receptor 13, having hydrogen bond donating
amide substituents in close proximity of the uranyl
center, in the membrane. This receptor combines a
reduced size of the cleft with the ability to donate
hydrogen bonds to the fluoride anion. The slope of the
response curve of -53 mV/decade is almost Nernstian,
and the detection limit is in the sub-millimolar range.
Sensors with ion receptor 13 have a 100-fold or higher
(12) van der Pol, J . F.; Neeleman, E.; Zwikker, J . W.; Nolte, R. J .
M.; Drenth, W. Recl. Trav. Chim., Pays-Bas 1988, 107, 615-620.
Pot
selectivity (log K
e -2) for fluoride over the other
F,j

Neutral Anion Receptors
J . Org. Chem., Vol. 62, No. 26, 1997 9037
solution was again cooled to 15 °C, 25 mL of fuming nitric acid
(100%) was slowly added, and the mixture was stirred at room
temperature for 3 days. The solution was poured into 250 g
of ice water, and the organic layer was washed with water (3
× 150 mL), saturated NaHCO3 solution (150 mL), and brine
(150 mL). After the mixture was dried with MgSO4, the
solvent was evaporated. Recrystallization from acetone yields
oxou r a n iu m (8): yield 0.30 g (45%); mp 144-145 °C; 1H NMR
(DMSO-d6) δ 9.40 (2H, s), 7.30 (4H, m), 7.16 (2H, d, J ) 7.1
Hz), 6.59 (2H, t, J ) 7.7 Hz), 4.14 (4H, t, J ) 6.3 Hz), 3.98
(6H, s), 1.80 (4H, m), 1.60-1.20 (36H, m), 0.84 (6H, t, J ) 6.4
Hz); 13C NMR (DMF-d7) δ 165.4 (d), 152.2 (s), 150.4 (s), 141.3
(s), 127.9 (d), 125.4 (s), 117.7 (s), 116.6 (d), 105.7 (d), 69.9 (t),
56.8 (q), 32.4 (t), 26.7 (t), 23.1 (t), 14.3 (q); MS-FAB 1013.4
((M + H)+, calcd 1013.5). Anal. Calcd C46H66N2O8U‚MeOH:
C, 54.0; H, 6.6; N, 2.7. Found: C, 53.6; H, 6.8; N, 2.9.
[[4,5-Bis(d od ecyloxy)-1,2-p h en ylen ebis[n itr ilom eth yli-
d yn e (2-h yd r oxy-5-m e t h oxyp h e n yl)]](2-)-N ,N ′,O,O′]d i-
oxou r a n iu m (9): yield 0.32 g (50%); mp 136-139 °C; 1H NMR
(DMSO-d6) δ 9.49 (2H, s), 7.40 (2H, s), 7.34 (2H, d, J ) 3.1
Hz), 7.24 (2H, dd, J ) 3.1 and 9.2 Hz), 6.90 (2H, d, J ) 9.2
Hz), 4.16 (4H, b), 3.76 (6H, s), 1.78 (4H, m), 1.60-1.20 (36H,
m), 0.85 (6H, t, J ) 6.4 Hz); 13C NMR (DMF-d7) δ 165.8 (d),
151.4 (s), 150.4 (s), 141.3 (s), 124.6 (d), 124.3 (s), 122.3 (s), 121.1
(d), 105.7 (d), 69.9 (t), 56.1 (q), 32.4 (t), 26.7 (t), 23.1 (t), 14.3
(q); MS-FAB 1014.0 ((M + H)+, calcd 1013.5). Anal. Calcd
C46H66N2O8U‚MeOH: C, 54.0; H, 6.6; N, 2.7. Found C, 54.0;
H, 6.8; N, 3.0.
[N,N′-[4,5-Bis(d od ecyloxy)-1,2-p h en ylen eb is[n it r ilo-
m eth ylid yn e(2-h yd r oxy-1,3-p h en ylen e)]a ceta m id e](2-)-
N,N′,O,O′]d ioxou r a n iu m (13): yield 0.23 g (30%); mp >300
°C; 1H NMR (DMSO-d6) δ 9.62 (2H, s), 9.20 (2H, s), 8.70 (2H,
s), 7.50 (2H, s), 7.49 (2H, s), 4.18 (4H, t, J ) 5.9 Hz), 2.37 (6H,
s), 1.79 (4H, m), 1.60-1.20 (54H, m), 0.85 (6H, t, J ) 6.4 Hz);
13C NMR (DMSO-d6) δ 168.1 (s), 165.4 (d), 156.8 (s), 149.3 (s),
139.9 (s), 138.3 (s), 129.4 (s), 125.1 (d), 121.9 (d), 105.1 (d),
68.9 (t), 33.7 (s), 31.4 (t), 31.3 (q), 29.1 (t), 29.0 (t), 28.8 (t),
28.7 (t), 25.7 (t), 24.8 (s), 22.1 (t), 13.9 (q); MS-FAB 1179.6
((M + H)+, calcd 1179.6). Anal. Calcd C56H84N4O8U: C, 57.1;
H, 7.2; N, 4.8. Found: C, 57.0; H, 7.2; N, 4.8.
CHEMF ETs. Rea gen ts. High molecular weight (HMW)
PVC was obtained from Fluka. o-Nitrophenyl n-octyl ether
(o-NPOE) was synthesized according to a literature proce-
dure.14 Tetraoctylammonium bromide (TOAB) was purchased
from Fluka. THF was freshly distilled from sodium/benzophe-
none ketyl before use. The anion sodium salts were of
analytical grade (Fluka). All solutions were made with deion-
ized doubly distilled water. Buffer pH 4 was obtained from
Yokogawa. The measurements were carried out in solution
of 0.01 M 4-morpholinomethanesulfonic acid (MES, Fluka)
adjusted to the desired pH with NaOH.
F a br ica tion of CHEMF ETs. CHEMFETs were prepared
from ISFETs with dimensions of 3 × 4.5 mm fabricated in the
MESA cleanroom facilities (University of Twente, The Neth-
erlands). Details of the modification of the ISFETs with poly-
(hydroxyethyl methacrylate) hydrogel (polyHEMA) have been
described before.15 The modified ISFETs were mounted on a
printed circuit board, wire bonded, and encapsulated with
epoxy resin (Hysol H-W 796/C8 W795). The polyHEMA layer
of the CHEMFET was conditioned by immersion in a 0.1 M
solution of the primary ion at pH ) 4 (Yokogawa buffer). The
ion selective membranes were prepared by dissolving in 0.7
mL of THF approximately 100 mg of a mixture composed of
33 wt % PVC, 66 wt % o-NPOE, 1 wt % receptor, and 20 mol
% (with respect to the receptor) TOAB. The membrane was
deposited on the gate area of the CHEMFET by casting this
solution using a capillary. The solvent was allowed to
evaporate overnight.
1
4.0 g (75%) of 2: mp 83-84 °C; H NMR δ 7.29 (2H, s), 4.10
(4H, t, J ) 6.6 Hz), 1.87 (4H, m), 1.52-1.26 (36H, m),0.88 (6H,
t, J ) 6.4 Hz); 13C NMR δ 151.8 (s), 136.5 (s), 107.9 (d), 70.2
(t), 31.9 (t), 29.7 (t), 29.6 (t), 29.4 (t), 29.2 (t), 28.7 (t), 25.8 (t),
22.7 (t), 14.1 (q); MS-FAB m/z 538.1 ((M + 2H)+, calcd 538.4).
Anal. Calcd C30H52N2O6: C, 67.1; H, 9.8; N, 5.2. Found: C,
66.9; H, 9.9; N, 5.3.
1,2-Bis(d od ecyloxy)-4,5-d ia m in oben zen e (3). To a solu-
tion of 1.8 g (3.4 mmol) of 2 in 50 mL of ethanol, 0.1 g of 10%
Pd/C, and 6.3 mL (37 mmol) of hydrazine monohydrate were
added. After 1 night of refluxing, the hot solution was filtered
over Hyflo, while kept under N2. After cooling, the white
precipitate was filtered off and rinsed with cold, O2-free
methanol: yield 1.3 g (80%); mp 73-74 °C; 1H NMR δ 6.38
(2H, s), 3.90 (4H, t, J ) 6.6 Hz), 1.80 (4H, m), 1.52-1.26 (36H,
m), 0.88 (6H, t, J ) 6.4 Hz); 13C NMR δ 143.4 (s), 128.4 (s),
106.8 (d), 70.7 (t), 31.9 (t), 29.7 (2 × t), 29.6 (t), 29.5 (t), 29.4
(t), 26.1 (t), 22.7 (t), 14.1 (q); MS-EI m/z 476.4 (M+, calcd 476.4).
N-(2-Hyd r oxy-4-ter t-bu tylp h en yl)a ceta m id e (11). To a
solution of 1.25 g (8 mmol) of 2-amino-4-tert-butylphenol in
40 mL of dry toluene was slowly added 0.82 g (8 mmol) of acetic
anhydride. The solution was stirred overnight, and after
cooling, a white precipitate was collected: yield 1.5 g (90%);
mp 169-171 °C; 1H NMR δ 8.69 (1H, s), 7.78 (1H, s), 7.14 (1H,
d, J ) 8.0 Hz), 6.99 (1H, s), 6.94 (1H, d, J ) 8.4 Hz), 2.23 (3H,
s), 1.25 (9H, s); 13C NMR δ 170.6 (s), 146.3 (s), 143.6 (s), 124.8
(s), 124.4 (d), 119.4 (d), 119.1 (d), 34.0 (s), 31.4 (q), 23.7 (q);
MS-EI m/z 207.1 (M+, calcd 207.1). Anal. Calcd C12H17NO2:
C, 69.5; H, 8.3; N, 6.8. Found: C, 69.4; H, 8.2; N, 7.0.
N -(3-F o r m y l-2-h y d r o x y -4-t er t -b u t y lp h e n y l)a c e t a -
m id e (12). A mixture of 1.5 g (7.2 mmol) of 11 and 1.01 g
(7.2 mmol) of hexamethylenetetraamine (HMTA) was dissolved
in 150 mL of trifluoroacetic acid and refluxed for 3.5 d. After
the mixture was cooled to 60 °C, 9 mL water was added, and
the resulting mixture was stirred for 2.5 h. The mixture was
dissolved in 150 mL of EtOAc, brought to neutral pH with
NaHCO3, and washed with 150 mL of brine. Evaporation
yields the crude product, which could be purified using column
chromatography (SiO2, CH2Cl2/MeOH 98/2); 1.2 g (70%) of the
product was obtained as a red solid: mp 82-83 °C; 1H
NMR δ 11.31 (1H, s), 9.88 (1H, s), 8.77 (1H, d, J ) 2.2 Hz),
7.72 (1H, b), 7.28 (1H, d, J ) 2.2 Hz), 2.24 (3H, s), 1.34 (9H,
s); 13C NMR δ 197.0 (d), 168.5 (s), 147.9 (s), 143.4 (s), 127.1
(s), 124.7 (d), 123.4 (d), 119.1 (s), 34.5 (s), 31.2 (q), 24.9 (q);
MS-EI m/z 235.1 (M+, calcd 235.1). Anal. Calcd C13H17NO3:
C, 66.4; H, 7.3; N, 6.0. Found: C, 66.5; H, 7.4; N, 6.0.
Gen er a l P r oced u r e for t h e Syn t h esis of UO2 Sa lo-
p h en es 7, 8, 9, a n d 13. A solution of 1.3 mmol of the
appropriate aldehyde (salicyl aldehyde (4), 3-methoxysalicyl
aldehyde (5), 5-methoxysalicyl aldehyde (6), or 12) and 0.3 g
(0.65 mmol) of diamine 3 in 25 mL of methanol was refluxed
for 1 h. Subsequently 0.27 g (0.65 mmol) of UO2(OAc)2‚2H2O
was added, and refluxing was continued for another 1 h. The
precipitate was filtered off and washed with methanol to yield
7, 8, 9, and 13 as an orange or red solid.
CHEMF ET Mea su r em en ts. CHEMFETs were condi-
tioned in a 0.1 M solution of the sodium salt of the primary
ion for one night, before starting the measurements. The
output signal of the CHEMFETs was measured in a constant
drain-current mode (Id ) 100 µA), with a constant drain-
source potential (Vds ) 0.5 V).16 This was achieved using an
ISFET amplifier of the source-drain follower type (Electro
[[4,5-Bis(d od ecyloxy)-1,2-p h en ylen ebis[n itr ilom eth yli-
d yn e(2-h yd r oxyp h en yl)]](2-)-N,N′,O,O′]d ioxou r a n iu m
(7): yield 0.28 g (45%); mp 151-154 °C; 1H NMR (DMSO-d6)
δ 9.56 (2H, s), 7.79 (2H, d, J ) 3.0 Hz), 7.60 (2H, t, J ) 7.4
Hz), 7.46 (2H, s), 6.99 (2H, d, J ) 9.3 Hz), 6.73 (2H, t, J ) 7.5
Hz), 4.18 (4H, b), 1.79 (4H, m), 1.60-1.20 (36H, m), 0.85 (6H,
t, J ) 6.4 Hz); 13C NMR (DMSO-d6) δ 169.4 (s), 164.8 (d), 149.1
(s), 140.1 (s), 135.5 (d), 135.3 (d), 124.3 (s), 120.5 (d), 116.5
(d), 105.1 (d), 68.9 (t), 31.3 (t), 29.1 (t), 29.0 (t), 28.2 (t), 28.7
(t), 25.7 (t), 22.1 (t), 13.9 (q); MS-FAB 953.3 ((M + H)+, calcd.
953.5). Anal. Calcd C44H62N2O6U‚1.5H2O: C, 53.9; H, 6.6; N,
2.9. Found: C, 54.1; H, 6.6; N, 2.9.
(13) Dangerous Properties of Industrial Materials, 5th ed.; Sax, N.
I., Ed.; van Nostrand Reinhold Co.: New York, 1979; pp 1078-1079.
(14) Ikeda, I.; Yamazaki, H.; Konishi, T.; Okahara, M. J . Membr.
Sci. 1989, 46, 113-119.
(15) Sudho¨lter, E. J . R.; van der Wal, P. D.; Skowronska-Ptasinska,
M.; van den Berg, A.; Bergveld, P.; Reinhoudt, D. N. Anal. Chim. Acta
1990, 230, 59-65.
[[4,5-Bis(d od ecyloxy)-1,2-p h en ylen ebis[n itr ilom eth yli-
d yn e(2-h yd r oxy-3-m et h oxyp h en yl)]](2-)-N,N′,O,O′]d i-
(16) Bergveld, P. Sens. Actuators 1981, 1, 17-29.

9038 J . Org. Chem., Vol. 62, No. 26, 1997
Antonisse et al.
Medical Instruments, Enschede, The Netherlands). The de-
veloped membrane potential was compensated by an equal and
opposite potential via the reference electrode. A saturated
calomel electrode (SCE) was used as a reference, connected to
the sample solution via a salt bridge filled with 1.0 M LiOAc.
Small amounts of acetate that might leak from the salt bridge
do not cause interference, as was checked in a separate
experiment. For measurements, 10 CHEMFETs were placed
in beaker with 25 mL of the sample solution (0.01 M MES
and 0.1 M of the sodium salt of the interfering ion under
investigation). Small amounts of primary ion sodium salt
solution (stock solutions of 0.01 and 1.0 M for NaH2PO4 and
0.01 and 0.5 M for NaF) were added to the sample solution to
obtain a series of measurements at primary ion activities (a)
ranging from log(a) ) -6.1 to -1.1, with steps of 0.2. Before
and after the measurement series, the pH of the solution was
measured and proved to be constant. The response of the
CHEMFETs was monitored simultaneously, and the data were
collected and analyzed using an Apple IIGS microcomputer.
The response times of CHEMFETs are on the order of a few
hundred milliseconds and shorter than the measuring time.17
All equipment was placed in a dark and grounded metal box
in order to eliminate any effects from static electricity and
photosensitivity of the CHEMFETs. The potentiometric se-
lectivity coefficients, KPi,jot, were determined by the fixed
interference method (FIM) according to IUPAC recommenda-
tions.18 All concentrations were converted to single-ion activi-
ties, and the mean activity coefficient was obtained by the
extended Debye-Hu¨ckel equation. The measurements were
performed at a temperature of 22 °C in an air-conditioned
room.
Ack n ow led gm en t . The Technology Foundation
(STW), Technical Science Branch of The Netherlands
Organization for Scientific Research (NWO) is gratefully
acknowledged for financial support.
(17) van der Wal, P. D.; Sudho¨lter, E. J . R.; Reinhoudt, D. N. Anal.
Chim. Acta 1991, 245, 159-166.
(18) Buck, R. P.; Lindner, E. Pure Appl. Chem. 1994, 66, 2527-
2536.
J O9707040