Molecular recognition of aliphatic diamines by 3,3′- di(trifluoroacetyl)-1,1′-bi-2-naphthol

Article abstract of DOI:10.1021/jo402277p

The fluorescent responses of 3,3′-di(trifluoroacetyl)-1,1′-bi- 2-naphthol toward a variety of amines have been studied. It was found that the aliphatic primary 1,2- and 1,5-diamines can greatly enhance the fluorescence of this compound, but under the same conditions, primary, secondary, and tertiary monoamines cannot turn on the fluorescence of this compound. In addition, this compound was shown to be an enantioselective and diastereoselective fluorescent sensor for chiral diamines. UV absorption and NMR spectroscopic methods have been used to study the interaction of the sensor with amines. These studies have demonstrated that the intramolecular OH···O=C hydrogen bonding of the sensor is important for both the reactivity of its trifluoroacetyl group with the amines and its fluorescent responses. The interaction of both of the two amine groups of a diamine molecule with the sensor is essential for the observed fluorescent sensitivity and selectivity.

Full text of DOI:10.1021/jo402277p

Article
pubs.acs.org/joc
Molecular Recognition of Aliphatic Diamines by 3,3′-
Di(trifluoroacetyl)-1,1′-bi-2-naphthol
Shanshan Yu, Winston Plunkett, Michael Kim, Elaine Wu, Michal Sabat, and Lin Pu*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States
*
S Supporting Information
ABSTRACT: The fluorescent responses of 3,3′-di(trifluoroacetyl)-1,1′-bi-2-
naphthol toward a variety of amines have been studied. It was found that the
aliphatic primary 1,2- and 1,5-diamines can greatly enhance the fluorescence of this
compound, but under the same conditions, primary, secondary, and tertiary
monoamines cannot turn on the fluorescence of this compound. In addition, this
compound was shown to be an enantioselective and diastereoselective fluorescent
sensor for chiral diamines. UV absorption and NMR spectroscopic methods have
been used to study the interaction of the sensor with amines. These studies have
demonstrated that the intramolecular OH···OC hydrogen bonding of the sensor is important for both the reactivity of its
trifluoroacetyl group with the amines and its fluorescent responses. The interaction of both of the two amine groups of a diamine
molecule with the sensor is essential for the observed fluorescent sensitivity and selectivity.
INTRODUCTION
amines and diamines. This study has provided further
understanding of the use of the trifluoromethyl ketone-based
sensor for the molecular recognition of amines and diamines.
■
Trifluoromethyl ketones contain a highly electrophilic trifluor-
oacetyl group whose reactions with a variety of nucleophiles
have been utilized for the development of various types of
molecular sensors. In 1974, the use of a trifluoromethyl aryl
ketone for the selective electrochemical detection of carbonates
was reported by Herman. It was found that the nucleophilic
addition of carbonates to the highly electrophilic trifluor-
omethyl ketone was responsible for the selective detection.
Trifluoromethyl aryl ketone-based membranes were used as
RESULTS AND DISCUSSION
■
(
1
. Synthesis and Characterization of 3,3′-Di-
1
trifluoroacetyl)-1,1′-bi-2-naphthol [(S)-4]. We prepared
the 3,3′-trifluoromethyl ketone (S)-4 from (S)-1,1′-bi-2-
naphthol (BINOL) [(S)-1] according to Scheme 1. Protection
of (S)-1 with methoxymethyl (MOM) groups gave (S)-2 in
2
9
optical sensors for humidity and ethanol as reported by Simon
95% yield. Treatment of (S)-2 with n-BuLi followed by
3
in 1991. These sensors showed hypsochromic shifts of their
addition of ethyl trifluoroacetate produced (S)-3 as a yellow oil
in 62% yield. The MOM groups of (S)-3 were removed in the
absorption bands when water or ethanol was added to the
trifluoroacetyl group to disrupt the conjugation system.
Additional reports have appeared in recent years for the further
development of trifluoromethyl ketone-based absorption and
fluorescence sensors to recognize many nucleophilic species
such as alcohols, amines, and various anions. The use of a
binaphthyl-based chiral trifluoromethyl ketone to distinguish
the enantiomers of amino acids by NMR spectroscopic
methods was also reported by Anh in 2010. In spite of these
presence of CF COOH to generate the desired 3,3′-
3
di(trifluoroacetyl)-BINOL (S)-4 as an orange solid in 84%
yield. Compound (S)-4 gave a much greater specific optical
1
rotation than (S)-3. The H NMR spectrum of (S)-4 in CDCl
3
4
revealed a deshield proton signal at δ 10.51 for the hydroxyl
groups, consistent with a strong hydrogen-bonding interaction
with the carbonyl groups. The hydroxyl proton signals of
5
19
BINOL derivatives normally appear at δ <6. The F NMR
studies, however, no study on the use of trifluoromethyl
ketone-based molecules for enantioselective fluorescent recog-
nition was reported before our recent work. Enantioselective
spectrum of (S)-4 in CDCl displayed a singlet at δ −70.06.
3
The UV absorption properties of a methylene chloride
solution of (S)-4 are compared with those of the MOM-
protected compound (S)-3 in Figure 1. For (S)-3, the
6
fluorescent sensors are potentially useful for rapid chiral assays,
and significant progress has been made in this area over the past
−
1
−1
absorptions were observed at λ /nm (ε/M cm ) = 229
(
max
4
4
4
7
,8
5.8 × 10 ), 257 (4.4 × 10 ), 291 (1.7 × 10 ), and 357 (3.5 ×
3
decade.
We recently communicated the use of 3,3′-
1
M
0 ). For (S)-4, the absorptions were observed at λ /nm (ε/
max
di(trifluoroacetyl)-1,1′-binaphthol for the enantioselective
fluorescent recognition of a chiral diamine. We have
−1
−1
4
4
4
6
cm ) = 228 (4.5 × 10 ), 263 (5.2 × 10 ), 319 (3.0 × 10 ),
3
and 432 (4.8 × 10 ). As shown in the UV absorption spectrum
demonstrated that using this trifluoroacetyl-based chiral sensor
allowed a simultaneous determination of both the concen-
tration and enantiomeric composition of the chiral diamine. In
this paper, we report our detailed investigation of the
interaction of the trifluoroacetyl compound with a variety of
of (S)-3 in Figure 1, protection of the two hydroxyl groups of
Received: October 12, 2013
Published: November 27, 2013
©
2013 American Chemical Society
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Scheme 1. Synthesis of 3,3′-Di(trifluoroacetyl)-BINOL [(S)-4]
Figure 1. Comparison of the UV spectrum of (S)-4 with that of (S)-3
−5
in CH Cl (1.0 × 10 M).
2
2
(S)-4 led to the disappearance of the longest-wavelength
absorption at λmax = 432 nm. Thus, this long-wavelength
absorption can be attributed to the effect of the intramolecular
OH···OC hydrogen bonding in (S)-4. This hydrogen
bonding should form a more planar conjugated system, and it
could also make the hydroxyl group a better electron donor and
the carbonyl group a better electron acceptor in comparison
with those in (S)-3.
Figure 3. Fluorescence spectra of (S)-4 in various solvents (1.0 × 10−
M). (λexc = 343 nm, slit = 2.0/2.0 nm.)
5
THF/H O (1:1) caused large fluorescence enhancements.
However, addition of H O to the CH Cl or CHCl solution of
S)-4 did not affect its fluorescence, which could be attributed
to the limited solubility of H O in these solvents. It is
2
2
2
2
3
The fluorescence spectrum of (S)-4 was also compared with
(
−5
that of (S)-3 in CH Cl at 1.0 × 10 M. As shown in Figure 2,
2
2
2
interesting to observe that when there was very weak or no
emission, the solution was light yellow, but when there was
strong emission, the solution became colorless.
The quenched fluorescence of compound (S)-4 could be
attributed to an excited-state intramolecular proton transfer
process involving its intramolecular OH···OC hydrogen
11
bonding. Absorption of photons frequently changes the
12
electron distribution within a fluorophore. Aromatic alcohols
or protonated amines become more acidic in the excited state
than in the ground state because the electrons on the hydroxyl
group or protonated amine are shifted into the aromatic ring in
13
the excited state. Aromatic carboxylic acids and esters usually
become more basic in the excited state because electron
acceptors have vacant π* orbitals into which electrons can be
Figure 2. Fluorescence spectra of (S)-3 and (S)-4 in CH Cl (1.0 ×
2
2
transferred. In the case of 2-naphthol, pK decreases from 9.2 in
−
5
a
10
M). (λexc = 343 nm, slit = 2.0/2.0 nm.)
14
the ground state to 2.0 in the excited state. In acid solution,
the emission is from naphthol with an emission maximum at
357 nm. In basic solution, the emission is from the naphtholate
anion with an emission maximum at 409 nm. At intermediate
although the MOM-protected compound (S)-3 gave very
strong emission at λ = 495 nm, (S)-4 was not emissive at all.
The emission of (S)-3 is significantly red-shifted from that of
15
pH values, emission from both species is observed in water. It
has been shown that water clusters serves as proton acceptors,
which explains why naphtholate emission disappears in
10
BINOL observed at around 360 nm, which could be
attributed to its internal charge-transfer state arising from the
incorporation of the trifluoroacetyl electron acceptor. Appa-
rently, the intramolecular OH···OC hydrogen bonding of
16
nonaqueous solvents. When a molecule contains both the
proton donor and proton acceptor, excited-state proton transfer
within the molecule is facile since the transferring proton is very
close to the acceptor. For example, methyl 2-hydroxy-3-
naphtholate (MNA), which contains both the proton donor
and proton acceptor, is known to undergo an intramolecular
(
S)-4 quenches its fluorescence.
We studied the solvent effect on the fluorescence properties
of (S)-4. As shown in Figure 3, (S)-4 gave very little emission in
CH Cl , CHCl , and CH CN, moderate emission in THF and
2
2
3
3
1
7
DMSO, and very strong emission in MeOH. Changing the
solvent from CH CN to CH CN/H O (1:1) and from THF to
excited-state proton transfer reaction. The transferring
proton, which is already hydrogen-bonded with ester group,
3
3
2
1
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6
very easily moves to its adjacent oxygen atom in the excited
state. This theory can also be applied to compound (S)-4
because of its intramolecular hydrogen bonds. When methanol
or water is added to (S)-4, nucleophilic attack on the highly
electrophilic carbonyls could happen, which should change the
structure of the original intramolecular hydrogen bond and thus
change its fluorescent properties.
toward the two enantiomers of trans-cyclohexane-1,2-diamine.
We further studied the interaction of (S)-4 with the structurally
diverse amines and diamines listed in Figure 4. These
compounds include the tertiary, secondary, and primary
monoamines 8−15, the aliphatic diamines 16−20, the aromatic
diamine 21, and the stereoisomeric aliphatic diamines 22 and
23.
a. Fluorescence Study. When (S)-4 (1.0 × 10− M in
5
−3
CH Cl ) was treated with monoamines 8−15 (1.0 × 10 M),
2
2
very little change in the fluorescence was observed (Figure 5a).
However, when the aliphatic diamines 16−19 were used under
the same conditions, large fluorescence enhancements were
observed. Among these, ethylenediamine (16) and 1,5-
diaminopentane (19) generated greater fluorescence enhance-
ments than 1,3-diaminopropane (17) and 1,4-diaminobutane
Scheme 2 shows a proposed mechanism for the fluorescence
of (S)-4. In nonaqueous solution, the excited-state proton
(
=
(
18), and they produced dual emission signals for (S)-4, with λ
370 nm and 438 nm (sh) for 16 and λ = 384 nm and 438 nm
sh) for 19. Both diamines enhanced the short-wavelength
Scheme 2. Proposed Mechanism for the Fluorescence of (S)-
4
emission more than the long-wavelength emission. The
fluorescence enhancements by the other two diamines, 17
and 18, were only 3% of that by 16. The benzylic diamine 20
and the aromatic diamine 21 did not turn on the fluorescence
at all.
We compared the fluorescence responses of (S)-4 toward the
previously reported trans-cyclohexane-1,2-diamine isomers
(
R,R)-22 and (S,S)-22 with those toward meso-cis-cyclo-
hexane-1,2-diamine [(S,R)-22]. As shown in Figure 5b, these
three stereoisomers gave very interesting fluorescence enhance-
ments. All three isomers turned on the fluorescence of (S)-4
and showed dual emission at λ = 370 and λ = 438 nm, but the
1
2
fluorescent responses at the two emission wavelengths were
different. (R,R)-22 caused large fluorescence enhancements at
both λ and λ , with the intensity at λ being smaller than that at
1
2
1
transfer of (S)-4 upon irradiation could generate a nonemissive
species 5. In the presence of water, the hydrate compound 6
could be generated. The excited-state proton transfer of 6 upon
irradiation could generate naphthalate 7, which could be
emissive.
λ
2
. (S,S)-22 enhanced λ
enhancement at λ
greatly, and the enhancement at λ
1
greatly but resulted in a much smaller
. The meso isomer (S,R)-22 enhanced λ
was a little smaller. Similarly,
2
1
2
both enantiomers of chiral 1,2-diaminopropane 23 caused
significant fluorescence enhancement at both λ and λ , with
1
2
2
. Interactions of (S)-4 with Amines. Earlier, we
(R)-23 providing greater enhancement than (S)-23 at λ2
communicated our study of the fluorescent response of (S)-4
(Figure 5c).
Figure 4. Structures of the various amines investigated.
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−5
Figure 6. Plots of the I /I ratio for (S)-4 (1.0 × 10 M) in the
1
2
presence of varying concentrations of (R,R)-, (S,R)-, and (S,S)-22. (I1
and I are the fluorescence intensities at λ = 370 nm and λ = 438 nm,
2
1
2
respectively. Solvent: CH Cl . λ = 343 nm, slit = 2/2 nm.)
2
2
exc
Figure 5. Fluorescence spectra of (S)-4 (1.0 × 10−5 M) in the
presence of (a) various achiral amines 8−21, (b) three stereoisomers
−3
of 22, and (c) two enantiomers of 23 (1.0 × 10 M). (λ = 343 nm,
exc
slit = 2.0/2.0 nm.)
We studied the effect of the concentration of the three
stereoisomers of cyclohexane-1,2-diamine on I /I , the ratio of
1
2
the fluorescence intensities at the two emission wavelengths. As
shown in Figure 6, the I /I ratio remained constant while the
1
2
concentrations of these three stereoisomers varied, with I /I =
1
2
0.67 for (R,R)-22, 2.60 for (S,S)-22, and 1.38 for (S,R)-22.
Therefore, using the value of the I /I ratio, we can distinguish
1
2
the three stereoisomers of cyclohexane-1,2-diamine without the
need to determine their concentrations.
A similar study was also conducted on the fluorescence
response of (S)-4 toward the chiral diamine 23 in the
−
4
−3
concentration range of 5.0 × 10 to 5.0 × 10 M. Plots of
−
5
the fluorescence intensity of (S)-4 at λ1 versus the
Figure 7. Plots of (a) I , (b) I and (c) I /I for (S)-4 (1.0 × 10 M)
1
2
1
2
concentrations of (R)- and (S)-23 (Figure 7a) show that I is
strongly dependent on the concentration of the diamine but
not on its chiral configuration. Plots of the fluorescence
in the presence of varying concentrations of (R)- and (S)-23. (I and I
1
1 2
are the fluorescence intensities at λ
= 370 nm and λ = 438 nm,
1 2
respectively. Solvent: CH Cl . λ = 343 nm, slit = 2/2 nm.)
2
2
exc
intensity at λ versus the concentrations of (R)- and (S)-23
2
(
Figure 7b) show significant enantioselectivity for this emission
In order to better understand the origin of the dual emission
responses of (S)-4 when treated with the diamines, excitation
spectra were recorded for (S)-4 in the presence of (R,R)- and
(S,S)-22. As shown in Figure 8, for each sample, the same
signal. We also found that the I /I ratio remained at 3.3−3.7
for (S)-23 and 2.3−2.1 for (R)-23 over the concentration range
1
2
of 5.0 × 10− to 5.0 × 10 M.
4
−3
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Figure 8. Excitation spectra of (S)-4 in CH Cl (1.0 × 10 M) in the presence of (a) (R,R)- or (b) (S,S)-22 (4.0 × 10−3 M). (Slit = 2.0/2.0 nm.)
−
5
2
2
excitation spectrum was obtained for emission at either 370 or
38 nm. This indicates that the emissions at the two
Scheme 3. Proposed Reaction of (S)-4 with Ethylenediamine
4
wavelengths should result from excitation of the same
ground-state species. The fluorescence lifetimes of (S)-4 in
the presence of chiral diamine 22 were measured and found to
be 1 ns for the emission at 370 nm and 1.7 ns for the emission
at 438 nm. The difference in the lifetimes suggests that the two
emission peaks should be from two different emitting states.
b. UV Study. We studied the effect of the amines on the UV
absorptions of (S)-4 in CH Cl . For monoamines 8−15 and
2
2
diamines 20 and 21, the UV spectra of the mixtures are simple
additions of that of (S)-4 with those of the amines. Thus, these
compounds did not cause significant changes in the absorption
of (S)-4. Aliphatic diamines 16−19 and the three stereoisomers
of chiral diamine 22 caused big changes in the UV absorptions
of (S)-4 with similar patterns (Figures S2 and S3 in the
Supporting Information). They included a significant decrease
in the absorbance intensity at λmax = 263, 319, and 432 nm, an
increase at 231 nm, and the appearance of a new absorption
peak at 345 nm. This demonstrates that these aliphatic
diamines generated significant structural changes of (S)-4 in
the ground state. The decreased absorption at the longest-
wavelength absorption of (S)-4 indicates the disruption of the
conjugation of the chromophore upon the addition of the
diamine.
converted to the aminal . After 108 equiv of the amine had been
added over 2 h, there was still an intense peak at δ −83.44
(
shifted slightly from δ −83.53 in the presence of the excess
amine). After the solution was allowed to stand overnight, the
hemiaminal signal was significantly reduced while the aminal
signal was increased, indicating that the conversion from the
hemiaminal 25 to the aminal 27 proceeded slowly.
c. NMR Study. We conducted 19F NMR titrations of (S)-4
The formation of the 1:2 adduct between (S)-4 and
ethylenediamine (16) as shown in Scheme 3 is consistent
with the Job plot obtained for the fluorescence response of (S)-
with 16, 19, and the three stereoisomers of 22 in CDCl . The
3
CDCl solution of (S)-4 (0.4 mL, 5.0 mM) was prepared in an
3
NMR tube. The CDCl solution of the diamine (1 mL, 0.5 M)
3
4
with the diamine at a total concentration of 0.1 mM (Figure
was prepared in a small vial as a stock solution. The NMR
spectrum of (S)-4 was first recorded, and then the stock
solution of the diamine was gradually added to the NMR tube.
After each addition, the solution was mixed well and the NMR
spectrum was recorded.
9
). This plot demonstrates that the fluorescence emission
reached a maximum at ∼30% (S)-4 for its interaction with the
diamine, indicating a (S)-4:16 binding stoichiometry of 1:2.
The NMR titration of (S)-4 with the three stereoisomers o6f
2
2 exhibited responses similar to those with ethylenediamine.
1
9
(
S)-4 showed a singlet F signal at δ −70.06. With the
As shown in Scheme 4, we observed that the reaction of (S)-4
with (S,S)-22 gave hemiaminal 28 quickly. Compound 28 was
addition of 0.2 equiv of 16, two peaks at δ −69.98 and −83.64
appeared with the same integration. These two new peaks kept
increasing while the signal at δ −70.06 decreased until 0.8 equiv
of 16 had been added. These two peaks were assigned to the
monohemiaminal product 24 on the basis of a comparison with
16
the literature data (Scheme 3). Next, a new peak at δ −83.53
started to show up and all of the other signals decreased until
7.1 equiv of 16 had been added, at which point all of the other
signals were converted to the peak at δ −83.53. This signal was
18
assigned to the dihemiaminal product 25. Further addition of
amine generated new peaks at around δ −72.58 and −80.20,
19
20
which were assigned to the imine 26 and the aminal 27,
respectively. The signal at δ −72.58 remained at low intensity
all the time, and the signal at around δ −80.20 increased while
the signal at δ −83.53 decreased. This indicates that once the
hemiaminal was converted to the imine, the imine was quickly
Figure 9. Job plot for the fluorescent response of (S)-4 with
ethylenediamine (16) (total concentration = 0.1 mM, λexc = 343 nm,
slit = 2.0/2.0 nm).
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Scheme 4. Proposed Mechanism for the Reaction of (S)-4
with (S,S)-22
Scheme 5. Proposed Reactions between (S)-4 and 1,5-
Diaminopentane
possible structure for the 1:1 adduct that could be generated
from the addition of one molecule of the diamine to both of the
then converted to imine 29 slowly over 12 h and then to aminal
COCF groups of (S)-4. Other products such as 32, imines,
3
1
9
30 over several days. Compound 30 can be prepared by
and oligomers could also be generated to give the complex
NMR spectrum.
F
carrying out the reaction of (S)-4 with (S,S)-22 in the presence
of molecular sieves at room temperature. The fluorescence
spectrum of the aminal product 30 was obtained, and it
d. X-ray Structures. Crystals of the aminal product 30
isolated from the reaction of (S)-4 with (S,S)-22 were obtained
by slow evaporation of its chloroform solution and used for X-
ray analysis. Crystals of the final addition products for the
reactions of (S)-4 with ethylenediamine (16) and propylenedi-
amine (17) were obtained by mixing the sensor with the
diamines in a 1:10 ratio in chloroform followed by slow
evaporation. The X-ray analyses of these crystals confirmed
their bis(cyclic aminal) structures, as shown in Figure 11 for 30.
In these structures, the dihedral angles of the binaphthyl units
are all 110°.
contained a single emission peak at λ = 383 nm in CH Cl with
2
2
stronger intensity than those of the intermediates.
The NMR titration of (S)-4 with 1,5-diaminopentane (19)
showed more complicated signal changes. With addition of 0.19
equiv of 19, a new peak at δ −83.81 appeared, and the signal of
(
S)-4 became a little broader; it continued to become broader
and shifted upfield with more amine addition. After the
addition of 0.94 equiv of 19, two new peaks at δ −85.80 and
−
86.65 appeared. When the amount of added amine increased
to 5.3 equiv, the broad peak completely disappeared and only
three peaks at δ −83.80, −85.81, and −86.41 were left. When
even more amine was added, the NMR spectrum became more
complex. The Job plot for the fluorescent response of (S)-4
toward 19 at a total concentration of 0.1 mM was obtained. As
shown in Figure 10, the maximum fluorescence was observed at
e. Discussion of the Interactions of (S)-4 with the
Diamines. Our study of the interactions of (S)-4 with various
amines demonstrated that the reactions of (S)-4 with aliphatic
primary diamines are much more facile than those with other
amines and give large fluorescence enhancements. The
Figure 10. Job plot for the fluorescent response of (S)-4 with 19 (total
concentration = 0.1 mM, λexc = 343 nm, slit = 2.0/2.0 nm).
50% (S)-4 for the interaction with 19, and the fluorescence
emission stayed high in the range of 30−50% (S)-4. This
indicates a complicated binding mode between (S)-4 and 19,
and both 1:1 and 1:2 (S)-4:19 binding stoichiometries could
exist in this system.
Thus, (S)-4 should have multiple modes of reaction with 19.
Scheme 5 shows some possible reaction pathways that could
lead to 1:1 and 1:2 adducts. Compound 31 represents one
Figure 11. X-ray structure of the aminal product of (S)-4 with (S,S)-
22.
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Scheme 6. Proposed Mechanism for the Reaction of (S)-4 with a 1,2-Diamine
fluorescence responses of (S)-4 toward the 1,2- and 1,5-
diamines are much greater than those toward the 1,3- and 1,4-
diamines. It is proposed that the intermolecular hydrogen bond
between one of the amine groups of a 1,2-diamine molecule
with the hydroxyl groups of the sensor, as shown by 33 in
Scheme 6, should facilitate the addition of the second amine
group to the trifluoroacetyl group. In the resulting adducts 34
and 35, the original O−H···OC hydrogen bonds in (S)-4
have been disrupted to generate the observed fluorescence
enhancement. That is, although the O−H···OC hydrogen
bonds of the sensor completely quench its fluorescence, the
new O−H···N hydrogen bonds do not. The multiple hydrogen
bonds shown by 35 could also contribute to the fluorescence
enhancement through the increased structural rigidity. The
interaction of both of the amine groups of the diamine with the
sensor as shown in 35 could also explain the observed highly
stereoselective fluorescent responses in the recognition of
cyclohexane-1,2-diamine. That is, the chirality around the
amine groups should lead to significant differences in the
stability of the diastereomeric adducts 35, giving the observed
stereoselective fluorescent responses. When the 1,3- and 1,4-
diamines are used, there may be greater ring strain for the
hydrogen-bonding interactions of the second amine with the
BINOL hydroxyl groups in the corresponding interactions
similar to 33−35, leading to the reduced fluorescence
enhancements. When the 1,5-diamine was used, the observed
large fluorescence enhancement could be attributed to the
formation of a compound like 31 where both carbonyl groups
of the sensor react with the amine to generate a more rigid
macrocyclic structure.
Figure 12. (a) Fluorescence spectra of (S)-3 in the presence of (R,R)-
or (S,S)-22 (λexc = 343 nm, slit = 2.0/2.0 nm). (b) UV spectra of (S)-3
−5
in the presence of (R,R)- or (S,S)-22. [(S)-3: 1.0 × 10 M in CH Cl .
2
2
−3
Amine: 5.0 × 10 M.)
trifluoroacetyl group of (S)-4, the hydrogen bonds of the
second amine group with the hydroxyl groups of (S)-4 could
increase the structural rigidity of the diamine addition products
to further enhance the fluorescence.
When the excitation wavelength was changed to 290 nm, the
MOM-protected compound (S)-3 showed dual emissions at λ
f. Interaction of the MOM-Protected Compound (S)-3 with
2. We also studied the interaction of the MOM-protected
2
=
359 and 494 nm, in which the emission at 359 nm was much
compound (S)-3 with the chiral diamines (R,R)- and (S,S)-22
in CH Cl . Without the intramolecular OH···OC hydrogen
weaker than that at 494 nm (Figure 13). We attribute the short-
wavelength emission to the locally excited state of the naphthol
units and the long-wavelength emission to the internal charge-
transfer state of the conjugated donor (OMOM) and acceptor
2
2
bonds of (S)-4, (S)-3 was strongly emissive. Both enantiomers
of 22 only slightly quenched the fluorescence of (S)-3 (by
∼
10%) with no enantioselectivity (Figure 12). The UV
spectrum of (S)-3 showed little change in the presence of
R,R)- or (S,S)-22. This demonstrates that without the
(
hydroxyl groups, there was little reaction between the amine
group and the trifluoroacetyl group. Thus, the hydroxyl groups
of (S)-4 could play multiple roles in the fluorescent recognition
of the diamines, as listed below: (1) They form intramolecular
hydrogen bonds with the carbonyl groups to quench the
fluorescence of (S)-4, which can then be turned on upon
interaction with the diamine. (2) These intramolecular
hydrogen bonds could activate the carbonyl groups for the
nucleophilic addition of the diamine. (3) The hydroxyl groups
can form intermolecular hydrogen bonds with one of the amine
groups of the diamine to accelerate the reaction. (4) After the
addition of one of the amine groups of the diamine to the
−5
Figure 13. Fluorescence spectra of (S)-3 in CH Cl (1.0 × 10 M) in
2
2
−
3
the presence of (R,R)- or (S,S)-22 (5.0 × 10 M) at λexc = 290 nm
(slit = 2.0/2.0 nm).
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COCF ) units. Only very small changes were observed at both
Article
(
emission (λ = 436 nm) of the sensor was also observed. At high
concentrations of propylamine, the UV absorptions of (S)-4
underwent significant changes. As shown in Figure 14b, in the
presence of 5.0 × 10− M propylamine, the long-wavelength
absorption of (S)-4 at λ = 432 nm diminished, accompanied by
the appearance of a new peak at 348 nm and decreases at 263
and 319 nm. These changes were very similar to those observed
for the interaction of 16 and 22 with (S)-4. These results
suggest that monoamines and diamines should cause similar
structural changes to (S)-4 but that much higher concentrations
are needed for the use of the monoamines.
3
wavelengths in the presence of 22.
g. Further Study of the Interaction of (S)-4 with
Propylamine at High Concentrations. As discussed above,
the aliphatic primary diamines such as 16, 19, and 22 reacted
with (S)-4 readily to greatly enhance its fluorescence. However,
2
−3
the monoamines at 1.0 × 10 M could not turn on the
fluorescence of (S)-4, as shown in Figure 5a. At this
concentration, they also did not cause any change in the UV
spectrum of (S)-4. In order to gain additional understanding of
the reaction of (S)-4 with the amines, we explored the use of
much higher concentrations of a monoamine, propylamine
We conducted an 19F NMR study of the reaction of (S)-4
with propylamine. For the NMR study, a much higher
(12), to interact with (S)-4. Figure 14a shows that when the
concentration of (S)-4 (5 mM) in CDCl than used in the
3
fluorescence and UV experiments (10− M) was needed for the
5
signal detection. However, at this high concentration, when
(
S)-4 was treated with propylamine, the NMR spectrum
showed the disappearance of the signal of (S)-4 with formation
of a very weak and broad signal. Sometimes the formation of a
yellowish precipitate could be observed. This indicates that the
solubility of the addition product of (S)-4 with propylamine
should be lower than the detection limit of the NMR
experiments for characterization. In order to characterize the
product of the reaction of (S)-4 with propylamine, we switched
1
9
the solvent to DMSO-d for the F NMR titration of (S)-4
6
19
with propylamine. In DMSO-d , the F NMR spectrum of (S)-
6
4
showed multiple signals, probably due to the reaction of the
nucleophilic solvent and water molecules with the trifluor-
oacetyl groups of (S)-4. Addition of 20 equiv of propylamine
1
13
converted all of the signals to a singlet at δ −81.51. H and C
NMR spectra for the reaction of (S)-4 with propylamine in
DMSO-d suggested a dihemiaminal structure for the reaction
6
product 36 (see page S32 in the Supporting Information). The
mass spectrum of the compound indicated that compound 36
might not be stable upon isolation, with a base peak at m/z
5
38.1 attributed to the loss of one of the two propylamine
groups of 36 (see page S33 in the Supporting Information).
Figure 14. (a) Fluorescence spectra of (S)-4 (1.0 × 10−5 M in
CH Cl ) in the presence of propylamine at 0−0.05 M (λ = 343 nm,
2
2
exc
−5
slit = 2.0/2.0 nm). (b) UV−vis absorption spectra of (S)-4 (1.0 × 10
M in CH Cl ) in the presence of propylamine at 0−0.05 M.
2
2
−
3
concentration of propylamine was increased over 5.0 × 10 M,
On the basis of these studies, the mechanism shown in
Scheme 7 is proposed to explain the fluorescence responses of
(S)-4 toward propylamine shown in Figure 14a. The observed
initial fluorescence enhancement of the short-wavelength
emission (λ = 380 nm) could be attributed to the formation
of the hemiaminal adduct 36. Further interaction of this adduct
−5
the fluorescence of (S)-4 (1.0 × 10 M in CH Cl ) at λ = 380
2
2
nm could be turned on, although the overall intensity was still
much weaker than that in the presence of the aliphatic
diamines. As the concentration of propylamine increased, a
significant fluorescence enhancement of the long-wavelength
Scheme 7. Proposed Interaction of (S)-4 with Propylamine
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The Journal of Organic Chemistry
Article
with additional amine molecules to form a hydrogen-bonded
complex such as 37 could contribute to the observed
fluorescence enhancement of the long-wavelength emission (λ
Synthesis and Characterization of (S)-3. Under nitrogen, 2,2′-
bis(methoxymethyl)-1,1′-binaphthyl [(S)-2] (3.0 mmol, 1.12 g) was
dissolved in diethyl ether (36 mL). The solution was cooled to 0 °C,
and n-BuLi (12.0 mmol, 2.5 M in hexane, 4.8 mL) was added
dropwise. The reaction mixture was stirred for 2 h at room
temperature and cooled to 0 °C, and then ethyl trifluoroacetate
=
436 nm).
The study of the fluorescent response of (S)-4 toward
propylamine at high concentrations could be used to explain
the observed dual emissions of (S)-4 in the presence of the
aliphatic diamines. That is, the nucleophilic addition of one
amine group of a diamine molecule to the trifluoroacetyl group
of (S)-4 should be responsible for the fluorescence enhance-
ment at the short wavelength, while the hydrogen-bonding
interaction of the second amine group of the diamine with the
hydroxyl groups of the sensor should be responsible for the
fluorescence enhancement of the long-wavelength emission.
(
13.5 mmol, 1.6 mL) was added slowly. The reaction mixture was
allowed to warm to room temperature and stirred for 1 h to afford a
creamlike mixture. A saturated aqueous NH Cl solution was added to
4
quench the reaction. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The combined
organic extracts were washed with brine and dried over Na SO . After
2
4
evaporation of the solvent, the residue was purified by column
chromatography on silica gel eluted with hexane/methylene chloride
(
1/3) to afford compound (S)-3 as a yellow oil in 62% yield (1.86
1
mmol, 1.05 g). H NMR (300 MHz, CDCl ): δ 2.77 (s, 6H), 4.73 (d, J
3
=
6.3 Hz, 2H), 4.77 (d, J = 6.3 Hz, 2H), 7.25 (d, J = 8.7 Hz, 2H),
SUMMARY
7.44−7.50 (m, 2H), 7.53−7.58 (m, 2H), 8.05 (d, J = 8.1 Hz, 2H), 8.43
■
s, 2H). 19F NMR (282 MHz, CDCl ): δ −73.62. C NMR (75 MHz,
13
(
3
We have demonstrated that the trifluoromethyl BINOL ketone
S)-4 is not only an enantioselective fluorescent sensor for
chiral 1,2-diamines but can also be used to distinguish aliphatic
,2- to 1,5-diamines from aromatic diamines and primary,
secondary, and tertiary monoamines. This study has shown that
the intramolecular OH···OC hydrogen bonding of the sensor
is important for both the reactivity of the trifluoroacetyl group
with the amines and the fluorescent response of the sensor. The
interaction of both of the amine groups of a diamine molecule
with the sensor is essential for the observed fluorescent
sensitivity and selectivity. This work has shed new light on the
trifluoromethyl ketone-based molecular sensors.
CDCl ): δ 56.6, 100.7, 116.5 (q, J = 290 Hz), 126.4, 126.8, 126.9,
3
(
1
27.0, 129.6, 129.8, 130.1, 132.7, 136.2, 151.6, 182.4 (q, J = 35.6 Hz).
+
HRMS Calcd for C H O F Na (MNa ): 589.1062. Found:
2
8
20
6 6
1
5
89.1053. [α] = −18.06 (c = 0.590, CHCl ).
D
3
Synthesis and Characterization of (S)-4. After compound (S)-3
(0.25 mmol, 134.2 mg) was dissolved in a minimum amount of
CH Cl , trifluoroacetic acid (1.0 mL) was added slowly, and the
2
2
mixture was stirred at room temperature for 10 min. A saturated
aqueous NaHCO solution was added to quench the reaction. The
organic layer was separated, and the aqueous layer was extracted with
CH Cl (3 × 20 mL). The combined organic extracts were washed
with brine and dried over Na SO . After evaporation of the solvent,
the residue was purified by column chromatography on silica gel eluted
3
2
2
2
4
with hexane/methylene chloride (2/1) to afford compound (S)-4 as
an orange solid in 84% yield (0.21 mmol, 100 mg). H NMR (300
1
EXPERIMENTAL SECTION
■
MHz, CDCl ): δ 7.16 (d, J = 7.5 Hz, 2H), 7.41−7.51 (m, 4H), 8.02 (d,
General Data. Reactions were carried out under nitrogen unless
otherwise noted. THF was distilled over sodium and benzophenone
under a nitrogen atmosphere. Methylene chloride and diethyl ether
were dried by passage through activated alumina columns under
nitrogen. Solvents were stored over 4 Å molecular sieves. Chemical
3
1
9
J = 7.5 Hz, 2H), 8.70 (s, 2H), 10.51 (s, 2H). F NMR (282 MHz,
CDCl ): δ −70.06. C NMR (150 MHz, CDCl ): δ 115.2, 116.7 (q, J
289.5 Hz), 117.8, 124.7, 125.3, 127.2, 131.2, 132.2, 136.1 (q, J = 3.75
13
3
3
=
Hz), 138.5, 155.0, 185.1 (q, J = 36.0 Hz). HRMS Calcd for
+
1
C H O F (MH ): 479.0718. Found: 479.0719. Mp: 231 °C. [α] =
4 6 D
shifts for H NMR spectra are reported in parts per million relative to
24 13
167.50 (c = 0.355, CHCl3).
Synthesis and Characterization of 30. Under nitrogen, (S)-4 (0.1
−
a singlet at 7.26 ppm for deuterated chloroform. Chemical shifts for
1
3
C NMR were reported relative to the center line of a triplet at 77.16
ppm for deuterated chloroform. The 19F NMR spectra are reported in
mmol, 47.8 mg) was dissolved in CH
2
Cl
2
(3 mL). (S,S)-22 (2.0 mmol,
́
2
28.4 mg) and 4 Å molecular sieves were added. The reaction mixture
parts per million relative to trifluoroacetic acid (δ −76.55) as an
external reference.
was stirred for 2 days at room temperature. After filtration, the solvent
was evaporated, and the residue was purified by column chromatog-
raphy on neutral aluminum oxide eluted with methylene chloride to
Preparation of Samples for Fluorescence Measurements.
Sensors were purified by column chromatography followed by
recrystallization and then stored in a refrigerator. All of the solvents
were either HPLC or spectroscopic grade. Stock solutions of the
sensors were freshly prepared for each measurement. For the
fluorescence study, a sensor solution was mixed with the amine
solution at room temperature in a 5 mL volumetric flask and diluted to
the desired concentration. The resulting solution was allowed to stand
at room temperature for 0.5 h before the fluorescence measurement,
and all of the fluorescence spectra were taken within 2 h.
1
afford compound 30 as a white solid in 65% yield. H NMR (300
MHz, CDCl ): δ 1.20−1.34 (m, 8H), 1.84−1.87 (m, 4H), 2.06−2.09
3
(
m, 2H), 2.25−2.29 (m, 2H), 2.47−2.58 (m, 8H), 7.27−7.29 (m, 6H),
19
7
.78−7.82 (m, 2H), 8.03 (s, 2H), 13.57 (s, 2H). F NMR (282 MHz,
13
CDCl ): δ −80.63. C NMR (150 MHz, CDCl ): δ 24.8, 24.9, 28.8,
3
3
2
9.5, 64.7, 65.4, 84.3 (q, J = 28.8 Hz), 117.7, 122.0, 123.4, 125.0, 125.7
(
q, J = 283.5 Hz), 127.5, 127.6, 128.5, 129.4, 134.5, 152.8. HRMS
+
Calcd for C H N O F (MH ): 671.2821. Found: 671.2831. Mp:
36
37
4
2 6
1
94 °C. [α] = −217.0 (c = 0.52, CHCl ).
D
3
Synthesis and Characterization of Compounds. Synthesis
and Characterization of (S)-2. Under nitrogen, (S)-BINOL [(S)-1]
(
17.5 mmol, 5.0 g) was dissolved in THF (200 mL). The solution was
ASSOCIATED CONTENT
Supporting Information
NMR spectra of new compounds, additional optical spectra,
and X-ray analysis data. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
cooled to 0 °C, and NaH (43.75 mmol, 60% in mineral oil, 1.75 g) was
added in small portions. The reaction mixture was stirred for 15 min,
and then chloromethyl methyl ether (43.75 mmol, 3.3 mL) was added
slowly. The reaction mixture was allowed to warm to room
temperature and stirred for 1 h. Water was added slowly to quench
the reaction. The organic layer was separated, and the aqueous layer
was extracted with ethyl acetate (3 × 30 mL). The combined organic
extracts were washed with brine and dried over Na SO . After
*
S
AUTHOR INFORMATION
Corresponding Author
E-mail: lp6n@virginia.edu.
■
*
2
4
evaporation of the solvent, the residue was purified by column
chromatography on silica gel eluted with hexane/ethyl acetate (15/1)
to afford compound (S)-2 as a white solid in 95% yield (16.6 mmol,
Notes
9
a
6
.22 g). The NMR data of the compound matched those reported.
The authors declare no competing financial interest.
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Article
ACKNOWLEDGMENTS
■
Partial support of this work from the U.S. National Science
Foundation (CHE-0717995 and CHE-1047104) is gratefully
acknowledged.
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