A novel cyanide chemodosimeter based on trifluoroacetamide benzhydrol-2 as binding motif: Importance of substituent positioning on intra-molecular charge transfer

Article abstract of DOI:10.1016/j.tet.2011.04.059

The nucleophilic nature of cyanide is used to develop a simple, sensitive, and highly effective sensor. Azo dye 6a based on 2-(trifluoroacetamide) benzhydrol-2 (2-TFAB) as anions receptor, presents a new way to build molecular color sensors for cyanide in

Full text of DOI:10.1016/j.tet.2011.04.059

Tetrahedron 67 (2011) 4196e4201
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A novel cyanide chemodosimeter based on trifluoroacetamide benzhydrol-2 as
binding motif: importance of substituent positioning on intra-molecular charge
transfer
,
b
,
a,b
Jalal Isaad a , Ahmida El Achari
*
a University Lille Nord de France, F-5900 Lille, France
b ENSAIT, GEMTEX Laboratory, F-59056 Roubaix, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The nucleophilic nature of cyanide is used to develop a simple, sensitive, and highly effective sensor. Azo
dye 6a based on 2-(trifluoroacetamide) benzhydrol-2 (2-TFAB) as anions receptor, presents a new way to
build molecular color sensors for cyanide in water. The 2-TFAB moiety of the dye 6a is used as receptor
group for cyanides and linked directly by dominant reversible covalent bonding over hydrogen bonding,
confirmed by the inactivity of the derivative 6b toward cyanides.
Received 28 February 2011
Received in revised form 4 April 2011
Accepted 15 April 2011
Available online 21 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Azo dye
Carbohydrate
Cyanides
Molecular charge transfer
Trifluoroacetamide
1. Introduction
coordination and transduction (i.e., the binding site and the sig-
naling subunit) are integrated into a superstructure.10
Considerable attention has been paid to the design and syn-
thesis of abiotic receptors for anionic species in the past two de-
cades, which makes anion recognition one of the fastest growing
disciplines in the field of supramolecular chemistry.1 In particular,
cyanide is one of the most toxic anions and is harmful to the en-
vironment and human health. Cyanide is widely used in industrial
fields due to its excellent chemical properties.2 It is used in organic
synthesis and in the making of plastics, in the recovery of gold and
silver from ores, and in the electroplating of metals, such as silver,
gold, platinum, and copper.3 Cyanide has long been known to be
a toxic substance,4 the toxicity of its salts exploited for many
hundreds of years. The detection of cyanides can be done in dif-
ferent ways. There are several methods for the detection and de-
termination of cyanides, such as spectrophotometic methods,5
electrochemical sensors,6 and fiber optic sensors,7 in addition to
indication formats, such as chemical displacement8 or molecular
chemodosimetry,4b,9 which requires an architecture in which the
two chemical entities responsible for the key actions of
Optical outputs are especially attractive with respect to the
transduction of a modulated signal, because detection can then use
cheap, easy-to handle and widely used instrumentation. Besides
fluorescence-based systems, colorimetric recognition has gained
popularity in recent years because a shift of an absorption band is
often intrinsically ratiometric and avoids the necessity for an in-
ternal reference and also offers the possibility of so-called ‘naked
eye detection’ for semiquantitative determinations.11
However, many receptors for cyanide reported to date have
several limitations as follows: (i) poor selectivity, especially in the
presence of fluoride or acetate, (ii) requiring specific conditions,
such as high temperature or basic media, (iii) not instantaneously
registering the addition of cyanide, (iv) requiring the use of in-
struments, such as luminoscopes, or UV light, (v) running the risk of
releasing HCN, (vi) only working in an organic environment, and
(vii) complicated synthesis. With these considerations in mind, we
now report a simple yet effective colorimetric sensor 2-(tri-
fluoroacetamide) benzhydrol-2 6a (2-TFAB), which overcomes the
above limitations, and can achieve the so-called ‘naked eye’ de-
tection of cyanide in an aqueous environment. Our strategy is based
on the fact that cyanide is a well known nucleophile and can attack
the carbon atom of an electron-deficient trifluoroacetyl group
easily by dominant reversible covalent bonding over hydrogen
* Corresponding author. Tel.: þ33 0320258936; fax: þ33 0320272597; e-mail
address: jalal.isaad@ensait.fr (J. Isaad).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.059

J. Isaad, A. El Achari / Tetrahedron 67 (2011) 4196e4201
4197
bonding (Fig. 1). Compounds 1-(trifluoroacetamide) benzhydrol 6b
(1-TFAB) and 2-(trifluoroacetamide) benzhydrol 6a (2-TFAB) were
also synthesized easily in five steps.
lmax¼447 nm (Fig. 2). To further investigate the selectivity of the
sensor 6a, 12 anions of interest, namely, CNꢁ, Fꢁ, AcOꢁ, H2PO4ꢁ, Clꢁ,
Brꢁ, Iꢁ, HSO4ꢁ, S2ꢁ, CO3ꢁ, Clꢁ, and N3 were added (as salts) to a so-
lution of 6a in pure water. It can be seen that only CNꢁ induced
a color change from colorless to yellow, and addition of other an-
ions caused no obvious changes either in color or in the UVevis
spectra, even in a large excess (Fig. 2).
Fig. 1. Structures of (trifluoroacetamide) benzhydrol-2-based receptor 2-TFAB 6a and
reference compound 1-TFAB 6b.
2. Results and discussions
2.1. Synthesis of chromogenic probes 6a and 6b
Scheme 1 report the synthesis of the azoic dye 6a possessing
(trifluoroacetamide) benzhydrol-2 as cyanide receptor.
Fig. 2. Absorption spectra when 2-TFAB 6a (50
mM) was treated with 2.0 equiv of
various anions: CNꢁ, Fꢁ, AcOꢁ, H2PO4ꢁ, Clꢁ, Brꢁ, Iꢁ, HSO4ꢁ, S2ꢁ, CO3ꢁ, Clꢁ, and N3 in pure
water at pH¼7.
The UVevis spectra changes and the corresponding color
changes of 6a toward anions are highly solvent sensitive, especially
to the amount of water present in the medium, probably due to the
strong solvation effect in water as demonstrated in our previous
studies.12 Consequently, a pure water system was used as the op-
timized condition for the titration experiments at room tempera-
ture (Fig. 3).
Scheme 1. Synthesis of the dye 6a. Reagent and conditions: (a) (CF3CO)2O, 80 ꢀC, 1 h
(b) NaBH4, EtOH, rt, (c) Aniline, NaNO2, HCl 37%, H2O, 0 ꢀC to rt, 12 h (d) NaH, THF, rt,
6 h (e) NaOMe, MeOH/CH3Cl, rt, 16 h.
3-Amino benzophenone 1a and trifluoroacetic anhydride was
stirred at 80 ꢀC for 1 h, and then the mixture was filtered and puri-
fied via column chromatography to afford compound 2a. The re-
duction the carbonyl group of compounds 2a to the corresponding
benzhydrol derivative 3a is carried out in the presence of NaBH4 in
the ethanol. The synthesis of the dye 4a was carried out by treating
the aniline with sodium nitrite in acidic medium at 0 ꢀC to form the
corresponding diazonium salt, followed by treatment with the de-
rivative 3a. The coupling of the bromo acetylated glucose de-
rivative13 and 4ain thepresence ofNaHasbase afford the dye 5a. The
chemosensor 6a was obtained by deprotection of 5a using NaOMe in
methanol in 89% as yield. Both compounds were characterized by 1H
NMR, 13C NMR, elemental analysis, and mass spectra.
Fig. 3. Suggested mechanism for offeon switching in the presence of CNꢁ anion.
To confirm the interaction mechanism between the cyanide and
the receptor 6a, 1H NMR titration experiments were carried out by
addition of Bu4NCN to a DMSO-d6 solution of 6a (Fig. 4). All the
aromatic protons exhibited an upfield shift, which is compatible
with the proposed switching mechanism.
Also, the 13C NMR of the adduct I present the disappearance of
the amidic CO signal at 155.11 of 6a and the appearance of two new
signals at 109.44 and 98.77 corresponding to CN and the formed
alcohol.
In the case of the reference compound 6b, addition of cyanide in
water produced no obvious color changes even in a large excess,
which can be ascribed to the strong intramolecular hydrogen bond
between the NH and the benzhydrol oxygen forming a six-
membered ring; hence the intermediate cyanohydrin cannot be
stabilized by the NH (Fig. 5).
2.2. Response to anions
In water, dye 6a shows a colorless solution with a maximum in
the absorption spectrum of 361 nm (
of cyanide to a solution of 6a in water (50 mM) causes a color change
from colorless to yellow accompanying a new absorption band at
3
¼32,950 Mꢁ1 cmꢁ1). Addition

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J. Isaad, A. El Achari / Tetrahedron 67 (2011) 4196e4201
Fig. 4. 1H NMR spectra of a solution of 6a in DMSO-d6 upon the addition of Bu4NCN.
Fig. 7. The plot of AꢁA0 versus equivalent of [CNꢁ] for the titration of 6a (50
CNꢁ (0e30 equiv) in water at 25 ꢀC and pH¼7.
mM) with
that dynamic quenching is a dominant process for the latter region
because molecular interactions other than collision are hard to
imagine between the adduct I and cyanide. The SterneVolmer plot
shown in Fig. 7 suggests that the dynamic quenching process may
be dominant but not exclusive.9u,v This absorbance intensity be-
havior depending on the cyanide equivalent also supports the for-
mation of a 1:1 adduct species I, and, furthermore, the absorbance
quenching is mainly due to the adduct formation.
Cyanide has the strongest carbonyl carbon affinity among the
anions examined, whereas anions, such as AcOꢁ and Fꢁ have lower
affinity and other anions have very weak affinity.12 The formation of
adduct I should be dependent on the anion’s carbonyl carbon affinity,
which led to the observed absorbance behavior dependent on the
anions. The fact that probe 6a recognizes anions through reversible
covalentadducts(RCA),notthroughH-bondinginteractions,themost
widely used paradigm in molecular recognition and sensing, suggests
that we may achieve a selectivity pattern completely different from
the absorbance probes based on H-bonding interactions in water. We
have shown that cyanide is preferably recognized by the 2-(tri-
fluoroacetamide) benzhydrol-2-based chemodosimeter. In addition,
cyanide has poor H-bonding ability compared to Fꢁ and AcOꢁ. Both
properties suggest that CNꢁ may be completely discriminated from
the competing Fꢁ and AcOꢁ if we use aqueous solvents. Indeed this is
the case. When probe 6a was titrated with the anions in water, only
CNꢁ showed significant absorbance quenching, and the competing
anions Fꢁ and AcOꢁ showed no changes (Fig. 2).
Fig. 5. Intramolecular hydrogen bond between eNH and the benzhydrol oxygen of 6b.
The binding constants calculated from a 1:1 stoichiometry using
nonlinear curve fitting analysis (see Supplementary data),14 based
on the absorption spectral changes at lmax¼447 nm, yields
K¼7.21ꢂ104 Mꢁ1 (Fig. 6).
The response time upon exposure to cyanide is instantaneous,
and the selectivity over Fꢁ and AcOꢁ is high (Fig. 8). This is very
important because Fꢁ and AcOꢁ are the main interfering ions in
cyanide sensing.
Fig. 6. A plot of 1/(AꢁA0) versus 1/[CNꢁ] at 447 nm in water. The concentration of the
chemosensor was 5 mM.
The colorimetric titration of probe 6a with CNꢁ (0e30 equiv)
gave an interesting quenching result, as inferred from a plot of
(AꢁA0) versus equivalent of the cyanide ion. Fig. 7 show a near linear
correlation between intensity difference absorption (AꢁA0) and CNꢁ
concentration in water at room temperature. This demonstrates the
potential utility of sensor 6a for calibrating and determining cyanide
ion concentration in water in the presence of other halide ions,
which did not cause any changes in the absorption of 6a.
The absorption spectra measured for the titration solutions with
increasing amounts of cyanide for the solutions containing 5,10, 20,
and 30 equiv of CNꢁ, respectively showed little spectral changes
from that of 6a, and only gradual hypsochromic shifts and very
small changes in the intensity were observed. Although further
experiments, such as luminescence lifetime measurements
depending on the concentration of quenchers can provide valuable
information on the quenching mechanism, we tentatively suggest
Fig. 8. Absorbance value changes (AꢁA0) of 6a (50
mM) at 447 nm in the presence of
30.0 equiv of selected anions in water at pH¼7. From the left: 6a only, CNꢁ, Fꢁ, AcOꢁ
,
H2POꢁ4 , Clꢁ, Brꢁ, Iꢁ, HSO4ꢁ, S2ꢁ, CO3ꢁ, Clꢁ, and N3.

J. Isaad, A. El Achari / Tetrahedron 67 (2011) 4196e4201
4199
The detection limit15 of cyanide in aqueous environment has been
calculated (see Supplementary data). Fig. 9 shows the plot of AꢁA0
versus the cyanide concentration in water. A linear response was ob-
served in the 0 to 1 cyanide equiv range. A detection limit as low as
Because of the reversibility of the nucleophilic addition of the
CNꢁ to the carbonyl group, the treatment of the adduct I with
MeOH/H2O causes the transformation of the cyanohydrins to the
carbonyl group by hydrolysis and the reformation of the double
bond between oxygen and carbon.
0.33
maximum allowed cyanide concentration in drinking water16
(1.9 M).
mM, the sensor 6a can be used to detect the WHO suggested
m
3. Conclusion
In summary, we have reported the use of 2-(trifluoroacetamide)
benzhydrol-2 as a chemodosimeter for the sensing of cyanide. The
probe recognizes cyanide through the formation of reversible co-
valent adducts, and gives selective absorbance quenching in water
among various anions examined. Our method is safe, fast, simple to
use, and inexpensive. The probe is easy to synthesize and allows
sensitive and highly selective detection of very low concentrations
of cyanide in an aqueous environment.
4. Experimental
4.1. Chemicals and materials
Fig. 9. A plot of (AꢁA0) versus CNꢁ concentrations at 447 nm in water at pH¼7. The
concentration of the chemosensor was 50 mM.
All chemicals and solvents obtained from commercial sources
As reported in previous study,17 the trifluoroacetyl group should
also interact with aliphatic amines or alcohols via nucleophilic at-
tack (Fig. 10).
were analytical pure and used without further purification. TLC was
ꢀ
carried out on silica gel pre-coated plates (Merck; 60 A F254) and
spots located with (a) UV light (254 and 366 nm), (b) ninhydrin
(solution in acetone), (c) fluorescamine, (d) I2 or (e) a basic solution
of permanganate [KMnO4 (3 g), K2CO3 (20 g), and NaOH (0.25 g) in
water (300 mL)]. Flash column chromatography (FCC) was carried
out on Merck silica gel 60 (230e400 mesh) according to Still et al.18
1H and 13C NMR spectra were recorded at 200 MHz with Varian
spectrometers in deuteriated solvents and are reported in parts per
million (ppm) with the solvent resonance used as the internal
reference. Mass spectra were recorded with a Thermo Fisher
LCQfleet ion-trap instrument (the spectra reported were also using
the ESI þc technique). Elemental analysis was carried out with
a PerkineElmer 240C Elemental Analyzer. UVevis spectra were
recorded with a Cary-4000 Varian spectrophotometer. The anions
CNꢁ, Fꢁ, AcOꢁ, H2PO4ꢁ, Clꢁ, Brꢁ, Iꢁ, HSO4ꢁ, S2ꢁ, CO3ꢁ, Clꢁ, and N3 are
coming from their corresponding salts KCN, KF, AcONa, Na(H2PO4),
KCl, KBr, KI, KHSO4, Na2S, Na2CO3, and NaN3.
Fig. 10. Nucleophilic attack of the alcohol and amine on the trifluoroacetyl group.
For this purpose, the sensing ability of 6a in water in the pres-
ence of 2-propanol, Ethanol as alcohols and 1-propylamine as
amine was evaluated. The addition of the 2-propanol, Ethanol, and
1-propylamine aqueous solutions (10ꢁ2 M) to the solution of
chromogenic probes 6a does not exhibit any significant shift, in-
sensitive to warming, stirring, powdering, and microwaving. Thus,
the chromogenic probe 6a can be used as water soluble chemo-
dosimeter for selective cyanide detection in pure water.
To evaluate the reversibility of adduct IeCNꢁ system, adduct I
was treated by increasing amounts of MeOH/H2O: 10/1 (0.25, 0.5,
0.75, 1.25, 1.5, and 2 mL). The complete disappearance of the ab-
sorbance spectrum at 447 nm and the appearance of the absorption
bond at 361 nm prove the transformation of adduct I to 6a (Fig. 11).
4.2. UVevis titrations
Stock solutions (1 mM) of the salts of (CNꢁ, Fꢁ, AcOꢁ, H2PO4ꢁ,
Clꢁ, Brꢁ, Iꢁ, HSO4ꢁ, S2ꢁ, CO3ꢁ, and N3) in water were prepared. Stock
solutions of chemodosimeter (0.1 mM) were prepared in water. Test
solutions were prepared by placing 4e40 mL of the probe stock
solution into a test tube, adding an appropriate aliquot of each
anion, and diluting the solution to 4 mL with water. All the exper-
iments were carried out at 20ꢃ2 ꢀC and pH¼7. After each addition
the UVevis spectra were taken and the absorbance values were
collected in water.
4.3. General procedures
4.3.1. General procedureA: synthesiscompounds 2a and 2b. Derivatives
(1a or 1b) were (1 equiv) dissolved in trifluoroacetic anhydride
(10 mL) and the resulting mixture was stirred at 80 ꢀC for 1 h. Then
the mixture was filtered and purified via column chromatography
(AcOEt/PE: 10/3) to afford the desired compounds 2a or 2b.
4.3.1.1. N-(3-Benzoylphenyl)-2,2,2-trifluoroacetamide (2a). The
product 2a was prepared according to the general procedure A
using the following quantities: 1a (1.00 g, 4.13 mmol), in tri-
fluoroacetic anhydride (10 mL). The crude material was purified by
FCC (EtOAc/petroleum ether, 10:3) to afford 2a (1.38, 99%). Rf¼0.63.
Fig. 11. Absorption spectra when adduct I was treated with increasing amounts of
MeOH/H2O.

4200
J. Isaad, A. El Achari / Tetrahedron 67 (2011) 4196e4201
1H NMR (200 MHz, CDCl3):
d
¼8.05e7.65 (m, 9H) ppm. 13C NMR
1 N/water (10 mL), to afford 4a (1.84 g, 89%). 1H NMR (200 MHz,
DMSO-d6):
¼8.11e7.94 (m, 4H), 7.71e7.39 (m, 9H), 5.77 (s, 1H) ppm.
13C NMR (50 MHz, DMSO-d6):
141.3, 137.6, 130.2, 129.7, 129.2, 128.4, 126.6, 123.4, 123.1, 120.7, 116.2,
115.1, 71.4 ppm. MS (ESI): m/z¼400.18 [Mþ1]þ. C21H16F3N3O2
(399.12): calcd C, 63.16; H, 4.04, found, C, 63.21; H, 4.08.
(50 MHz, CDCl3):
d¼193.5, 155.2, (CO), 144.1, 140.1, 138.1, 132.8,
d
132.3, 130.2, 128.5, 126.7, 125.5, 119.9 (ArH), 115.5 ppm. MS (ESI): m/
z¼294.07.16 [Mþ1]þ. C15H10F3NO2 (293.07): calcd C, 61.44; H, 3.44,
found, C, 61.49; H, 3.48.
d
¼155.1 (CO),152.0,149.1,146.4,143.0,
4.3.1.2. N-(2-Benzoyl-5-nitrophenyl)-2,2,2-trifluoroacetamide
(2b). The product 2b was prepared according to the general pro-
cedure A using the following quantities: 1b (1.00 g, 4.13 mmol), in
trifluoroacetic anhydride (10 mL). The crude material was purified
by FCC (EtOAc/petroleum ether, 10:3) to afford 2b (1.32, 95%).
4.3.3.2. Azo dye 4b. The product 4b was prepared according to
the general procedure C using the following quantities: aniline (0.5 g,
5.20 mmol), 3b (1.50 g, 5.20 mmol), NaNO2 (0.47 g, 6.24 mmol), in
HCl 1 N/water (10 mL), to afford 4b (1.82 g, 88%). 1H NMR (200 MHz,
Rf¼0.65. 1H NMR (200 MHz, CDCl3):
d
¼8.06e7.65 (m, 9H) ppm. 13
C
DMSO-d6):
d
¼8.11e7.93 (m, 4H), 7.73e7.37 (m, 9H), 5.76 (s,1H) ppm.
NMR (50 MHz, CDCl3):
d
¼193.6, 155.3, (CO), 139.4, 138.6, 132.8,
13C NMR (50 MHz, DMSO-d6):
d
¼155.7 (CO),152.3,148.4,144.5,143.8,
132.1, 130.2, 128.7, 127.6, 125.5, 124.6, 119.9 (ArH), 115.5 ppm. MS
(ESI): m/z¼294.19 [Mþ1]þ. C15H10F3NO2 (293.07): calcd C, 61.44; H,
3.44, found, C, 61.47; H, 3.49.
138.5, 130.4, 129.8, 129.4, 128.4, 126.5, 123.6, 123.1, 121.7, 115.1, 108.3,
71.2 ppm. MS (ESI): m/z¼400.21 [Mþ1]þ. C21H16F3N3O2 (399.12):
calcd C, 63.16; H, 4.04, found, C, 63.19; H, 4.07.
4.3.2. General procedure B: synthesis compounds 3a and 3b. To
a solution of 2a or 2b derivatives (1 mol) was dissolved in ethanol
(10 ml), NaBH4 (1 mol) was added and the resulting mixture was
stirred under reflux. After the completion of the reaction (moni-
tored by TLC), the reaction mixture was filtered through Celite. The
filtrate was evaporated under vacuum and the residue was taken
into chloroform, washed twice with 80% saturated brine solution
and finally with water. The organic layer was dried over anhydrous
sodium sulfate and evaporation of the organic layer was followed
by purification either by column chromatography, to yield the de-
sired products 3a or 3b.
4.3.4. General procedure D: synthesis of compounds 5a and 5b. To
a solution of 4a (1 mol) in 15 mL of THF, a solution of NaH (1 mol) in
THF (2 mL) was added dropwise at 0 ꢀC and the resulting mixture
was stirred for 30 min. The glucose derivative (1 mol) in THF (3 ml)
was added and the resulting mixture was stirred at room temper-
ature for 6 h. After this time, the reaction mixture was filtered
through Celite. The filtrate was evaporated under vacuum and the
residue was taken into chloroform, washed twice with 80% satu-
rated brine solution and finally with water. The organic layer was
dried over anhydrous sodium sulfate and evaporation of the or-
ganic layer was followed by purification either by column chro-
matography, to yield the desired products 5a or 5b.
4.3.2.1. N-(3-Benzoyl-5-aminophenyl)-2,2,2-trifluoroacetamide
(3a). The product 3b was prepared according to the general pro-
cedure B using the following quantities: 2b (1.00 g, 3.24 mmol),
NaBH4 (0.13 g, 3.24 mmol). The crude material was purified by FCC
(EtOAc/petroleum ether, 2:1) to afford 3b (0.94, 95%). Rf¼0.55. 1H
4.3.4.1. Azo dye 5a. The product 5a was prepared according to
the general procedure D using the following quantities: 4a (0.5 g,
1.25 mmol), NaH (0.03 g, 1.25 mmol), glucose derivative (0.51 g,
1.25 mmol) to afford 5a (0.82 g, 88%). 1H NMR (200 MHz, DMSO-
NMR (200 MHz, CDCl3):
NMR (50 MHz, CDCl3):
d
¼7.76e7.13 (m, 9H), 5.77 (s, 1H) ppm. 13
C
d6): see Table 1 for glucidic part and
(m, 9H), 5.77 (s, 1H), 2.25 (s, 12H) ppm. 13C NMR (50 MHz, DMSO-
d6): see Table 2 for glucidic part and
d
¼8.11e7.92 (m, 4H), 7.74e7.38
d
¼155.1 (CO), 143.3, 143.2, 139.5, 129.6,
129.1, 128.5, 126.4, 123.2, 120.7, 119.2 (AreH), 115.5, 70.2 ppm. MS
(ESI): m/z¼296.13 [Mþ1]þ. C15H12F3NO2 (295.08): calcd C, 61.02; H,
4.10, found, C, 61.06; H, 4.14.
d
¼170.4 (CO) 155.3 (CO), 152.1,
149.3, 146.4, 143.2, 141.4, 137.3, 130.5, 129.5, 129.6, 128.1, 126.2,
123.6, 123.2, 120.7, 116.3, 115.3, 71.1, 21.4 (CH3) ppm. MS (ESI): m/
z¼730.26 [Mþ1]þ. C21H16F3N3O2 (729.21): C, 57.61; H, 4.70, found,
C, 57.66; H, 4.75.
4.3.2.2. N-(2-Benzoyl-5-aminophenyl)-2,2,2-trifluoroacetamide
(3b). The product 3b was prepared according to the general pro-
cedure B using the following quantities: 2b (1.00 g, 3.24 mmol),
NaBH4 (0.13 g, 3.24 mmol). The crude material was purified by FCC
(EtOAc/petroleum ether, 2:1) to afford 2b (0.94, 95%). Rf¼0.57. 1H
4.3.4.2. Azo dye 5b. The product 5b was prepared according to
the general procedure D using the following quantities: 4b (0.5 g,
1.25 mmol), NaH (0.03 g, 1.25 mmol), glucose derivative (0.51 g,
1.25 mmol) to afford 5b (0.83 g, 89%). 1H NMR (200 MHz, DMSO-
NMR (200 MHz, CDCl3):
NMR (50 MHz, CDCl3):
128.7, 128.2, 126.6, 126.2, 124.9, 115.9, 115.2, 70.1 ppm. MS (ESI): m/
z¼309.33 [Mþ1]þ. C15H11F3N2O2 (308.26): calcd C, 58.45; H, 3.60,
found, C, 58.53; H, 3.67.
d
¼7.77e7.11 (m, 9H), 5.76 (s, 1H) ppm. 13
C
d
¼155.8 (CO), 144.4, 143.1, 136.6, 129.5,
d6): see Table 1 for glucidic part and
(m, 9H), 5.75 (s, 1H), 2.26 (s, 12H) ppm. 13C NMR (50 MHz, DMSO-
d6): see Table 2 for glucidic part and
d
¼8.13e7.93 (m, 4H), 7.74e7.37
d¼170.2 (CO), 155.5 (CO), 152.3,
148.3, 144.5, 143.7, 138.5, 130.5, 129.8, 129.5, 128.4, 126.4, 123.6,
123.1, 121.7, 115.1, 108.2, 71.4, 21.1 (CH3) ppm. MS (ESI): m/z¼400.24
[Mþ1]þ. C21H16F3N3O2 (399.12): calcd C, 63.16; H, 4.04, found, C,
63.20; H, 4.08.
4.3.3. General procedure C: synthesis compounds 4a and 4b. To
a solution aniline (1 mol) in 15 mL of water/HCl 1 N: 15/1.5, a so-
lution of NaNO2 (1.4 mmol) in water (2 mL) was added dropwise at
0 ꢀC and the resulting mixture was stirred for 30 min. The di-
azonium salt solution previously prepared was added dropwise to
the solution of 3a or 3b (1 mol) in methanol (3 ml) and the com-
bined solutions was maintained at 0 ꢀC for 6 h with stirring. After
this time, the pH was adjusted to 8 and the resulting mixture was
diluted with chloroform (20 ml), the formed product was isolated
by filtration and washed with chloroform to afford the corre-
sponding azo dyes 4a or 4b.
4.3.5. Generale procedure E: synthesis of 6a and 6b. The compounds
6a and 6b were then deprotected using the classic sodium meth-
oxide in MeOH method (1 equiv) stirring at room temperature for
16 h. Chloroform was used as a co-solvent where necessary for
complete solvation. Acidic ion-exchange resin (Amberlite IR-120)
was then added and at neutralization was filtered off and washed
with MeOH. The solvent was then evaporated off to afford the
products 6a and 6b.
4.3.3.1. Azo dye 4a. Theproduct 4awasprepared according tothe
general procedure C using the following quantities: aniline (0.5 g,
5.20 mmol),3a(1.50 g, 5.20 mmol),NaNO2 (0.47 g, 6.24 mmol), inHCl
4.3.5.1. Azo dye 6a. Hydrolysis of 5a (0.60 g, 0.83 mmol) with
sodium methoxide in MeOH (5 mL) by the procedure E afforded 6a
(0.45 g, 98% yield) as a mixture of a- and b-pyranosic anomers in

J. Isaad, A. El Achari / Tetrahedron 67 (2011) 4196e4201
4201
(e) Vennesland, B.; Comm, E. E.; Knownles, C. J.; Westly, J.; Wissing, F. Cyanide in
Biology; Academic: London, 1981.
the ratio of 40:60, calculated on the basis of the relative C-1 signal
intensities. 1H NMR (200 MHz, DMSO-d6):
d
¼8.11e7.92 (m, 4H),
5. (a) Deep, B.; Balasubramanian, N.; Nagaraja, K. S. Anal. Lett. 2003, 36, 2865; (b)
Geetha, K.; Balasubramanian, N. Anal. Lett. 2001, 34, 2507; (c) Wang, M.; Luo, D.
L. Chin. J. Anal. Chem. 2000, 28, 519; (d) Haj-Hussein, A. T. Talanta 1997, 44, 545;
(e) Ishii, H.; Kohata, K. Talanta 1991, 38, 511.
7.74e7.37 (m, 9H), 5.8 (d, 1H, J¼9.3 Hz), 5.76 (s, 1H), 5.55 (m, 2H),
5.22 (dd, 1H, J¼10.3, 3.3 Hz), 4.2 (m, 3H) ppm. 13C NMR (50 MHz,
DMSO-d6): see Table 3 for glucidic part and
d
¼155.4 (CO), 152.1,
€
6. (a) Keusgen, M.; Kloock, J. P.; Knobbe, D.-T.; Junger, M.; Krest, I.; Goldbach, M.;
149.2, 146.5, 143.2, 141.3, 137.5, 130.5, 129.5, 129.6, 128.1, 126.2,
123.6, 123.2, 120.6, 116.3, 115.4, 71.2 ppm. MS (ESI): m/z¼562.22
[Mþ1]þ. C27H26F3N3O7 (561.17): calcd C, 57.75; H, 4.67, found, C,
57.79; H, 4.71.
Klein, W.; Schoning, M. J. Sens. Actuators, B 2004, 103, 380; (b) Lindsay, A. E.;
O’Hare, D. Anal. Chim. Acta 2006, 558, 158; (c) Hassan, S. S. M.; Marzouk, S. A.
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Biotechnol. 1996, 48, 73; (h) Siontorou, C. G.; Nikolelis, D. P. Anal. Chim. Acta
1997, 355, 227.
4.3.5.2. Azo dye 6b. Hydrolysis of 5b (0.60 g, 0.83 mmol) with
sodium methoxide in MeOH (5 mL) by the procedure E afforded 6a
(0.47 g, 99% yield) as a mixture of
the ratio of 40:60, calculated on the basis of the relative C-1 signal
intensities. 1H NMR (200 MHz, DMSO-d6):
a- and b-pyranosic anomers in
7. (a) Jawad, S. M.; Alder, J. F. Anal. Chim. Acta 1991, 246, 259; (b) Freeman, M. K.;
Bachas, L. G. Anal. Chim. Acta 1990, 241, 119; (c) Bentley, A. E.; Alder, J. F. Anal.
Chim. Acta 1989, 222, 63.
d
¼8.13e7.94 (m, 4H),
ꢁ~
8. (a) García-Acosta, B.; Albiach-Martí, X.; García, E.; Gil, L.; Matínez-Manez, R.;
7.74e7.38 (m, 9H), 5.82 (d, 1H, J¼9.3 Hz), 5.76 (s, 1H), 5.56 (m, 2H),
ꢁ
Rurack, K.; Sancenon, F.; Soto, J. Chem. Commun. 2004, 774; (b) Ros-Lis, J. V.;
5.24 (dd, 1H, J¼10.2, 3.3 Hz), 4.2 (m, 3H) ppm. 13C NMR (50 MHz,
ꢁ~
ꢁ
Martínez-Manez, R.; Rurack, K.; Sancenon, F.; Soto, J.; Spieles, M. Inorg. Chem.
ꢁ
ꢁ~
ꢁ
2004, 43, 5183; (c) Jimenez, D.; Martínez-Manez, R.; Sancenon, F.; Ros-Lis, J. V.;
Soto, J.; Benito, A.; García-Breijo, E. Eur. J. Inorg. Chem. 2005, 2393; (d) Wiskur,
S. L.; Aït-Haddou, H.; Lavigne, J. J.; Anslyn, E. V. Acc. Chem. Res. 2001, 34, 963; (e)
Jimenez, D.; Martínez-Manez, R.; Sancenon, F.; Ros-Lis, J. V.; Benito, A.; Soto, J. J.
Am. Chem. Soc. 2003, 125, 9000; (f) Ros-Lis, J. V.; García, B.; Jimenez, D.; Mar-
tinez-Manez, R.; Sancenon, F.; Soto, J.; Gonzalvo, F.; Valldecabres, M. C. J. Am.
Chem. Soc. 2004, 125, 4064; (g) Ros-Lis, J. V.; Martínez-Manez, R.; Soto, J. Chem.
Commun. 2002, 2248; (h) Ros-Lis, J. V.; Martínez-Manez, R.; Soto, J. Chem.
DMSO-d6): see Table 3 for glucidic part and
d¼155.4 (CO), 152.2,
148.3, 144.5, 143.7, 138.6, 130.4, 129.9, 129.5, 128.4, 126.4, 123.6,
123.1, 121.7, 115.2, 108.3, 71.4 ppm. MS (ESI): m/z¼562.21 [Mþ1]þ.
C27H26F3N3O7 (561.17): calcd C, 57.75; H, 4.67, found, C, 57.80;
H, 4.72.
ꢁ
ꢁ~
ꢁ
ꢁ
ꢁ~
ꢁ
ꢁ~
ꢁ~
Commun. 2005, 5260.
Acknowledgements
9. (a) Kim, Y.-H.; Hong, J.-I. Chem. Commun. 2002, 512; (b) Liu, H.; Shao, X.-B.; Jia,
M.-X.; Jiang, X.-K.; Li, Z.-T.; Chen, G.-J. Tetrahedron 2005, 61, 8095; (c) Chow, C.-
F.; Lam, M. H. W.; Wong, W.-Y. Inorg. Chem. 2004, 43, 8387; (d) Zelder, F. H.
Inorg. Chem. 2008, 47, 1264; (e) Zeng, Q.; Cai, P.; Li, Z.; Qin, J.; Tang, B. Z. Chem.
Commun. 2008, 1094; (f) Todd, W.; Gabbaı, F. P. J. Am. Chem. Soc. 2007, 129,
This work is financially supported by GEMTEX LaboratorydFrance.
We thank Mr. Christian Catel (technician of GEMTEX laboratory) for its
kind disponibility.
€
ꢁ
3635; (g) Jin, W. J.; Fernandez-Arguelles, M. T.; Costa-Fernandez, J. M.; Sanz-
Medel, A. Chem. Commun. 2005, 883; (h) Touceda-Varela, A.; Stevenson, E. I.;
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Galve-Gasion, J. A.; Dryden, D. T. F.; Mareque-Rivas, J. C. Chem. Commun. 2008,
Supplementary data
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Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.04.059.
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