Relay recognition of F- and a nerve-agent mimic diethyl cyano-phosphonate in mixed aqueous media: Discrimination of diethyl cyanophosphonate and diethyl chlorophosphate by cyclization induced fluorescence enhancement

Article abstract of DOI:10.1039/c5ra24392k

Anion to nerve agent simulant detection by relay recognition has been designed and realized for the first time with sequence specificity (F^- → DCNP) via a fluorescence "off-on-on" mechanism. The discrimination of DCNP and DCP via a CIFE (cyclization induced fluorescence enhancement) mechanism has also been demonstrated here. Test strips based on the sensors with F^- and DCNP are fabricated, which can act as convenient and efficient nerve agent and F^- test kits. The origin of the sequence specificity of different fluorescence recognition was revealed through single X-ray crystal and NMR analysis.

Full text of DOI:10.1039/c5ra24392k

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PAPER
Relay recognition of Fꢀ and a nerve-agent mimic
diethyl cyano-phosphonate in mixed aqueous
media: discrimination of diethyl cyanophosphonate
and diethyl chlorophosphate by cyclization
induced fluorescence enhancement†
Cite this: RSC Adv., 2016, 6, 18711
a
a
Avijit Kumar Das, Shyamaprosad Goswami, Ching Kheng Quahb
*
and Hoong-Kun Funbc
Anion to nerve agent simulant detection by relay recognition has been designed and realized for the first
time with sequence specificity (Fꢀ
/ DCNP) via a fluorescence “off–on–on” mechanism. The
Received 18th November 2015
Accepted 1st February 2016
discrimination of DCNP and DCP via a CIFE (cyclization induced fluorescence enhancement) mechanism
has also been demonstrated here. Test strips based on the sensors with Fꢀ and DCNP are fabricated,
which can act as convenient and efficient nerve agent and Fꢀ test kits. The origin of the sequence
specificity of different fluorescence recognition was revealed through single X-ray crystal and NMR analysis.
DOI: 10.1039/c5ra24392k
www.rsc.org/advances
essential ingredient in toothpaste, pharmaceutical agent and
even its addition to drinking water due to their tendency to
prevent dental caries,5 enamel demineralization and for the
Introduction
Compared to the normal traditional chemosensor method
(displacement of a metal complex by anions1 and employment
of an ion-pair receptor through cooperative interactions among
co-bound ions and a heteroditopic host2) depending on the
nature and reactivity of the chemodosimetric centres, an alter-
native chemodosimeter approach3 based on an irreversible
specic chemical reaction has emerged as an active research
area of signicant importance recently. But the bi-functional
chemodosimetric centres, which refer to those based on
a single host platform that give distinct colorimetric and uo-
rescence responses independently by recognizing two different
guest species in the same or different channels, have gradually
become a new and fantastic research focus in the eld of uo-
rescence sensors specially by the chemodosimetric eld.4 On
this occasion, we have employed a single chemosensor which
selectively binds Fꢀ and DCNP in a relay manner by a different
chemical reaction based approach. As the smallest anion, Fꢀ
has unique chemical properties and it is widely used as an
treatment of osteoporosis.6 Based on the chemical affinity
between silicon and uoride, a variety of chemosensors has
recently undergone a quiet revolution7 and we have used this
uoride mediated de-silylation technique as the rst step of the
relay recognition phenomenon. On the other hand, nerve
agents are among the most important and lethal classes of
chemical-warfare agents (CWAs) and their use in terrorist
attacks has led to increasing interest in the development of
reliable and accurate methods to detect these lethal chemicals.8
Among CW species, nerve agents are especially hazardous and
can cause death within minutes aer exposure and the United
Nations classify them as weapons of mass destruction. Sarin,
Soman and Tabun are by far the most known chemical warfare
agents among the nerve gases in which the electrophilic centre
is easily attacked by different functional groups. Depending on
this specic chemical nature of these nerve gases and to over-
come the limitations to the different biochemical and instru-
mental methods (biosensors,9 ion mobility spectroscopy
(IMS),10 electrochemistry,11 micro-cantilevers,12 photonic crys-
tals,13 optical-bre arrays14), an alternative way for the devel-
opment of easy-to-use uorogenic and chromogenic
chemosensors for the detection of these gases have gained
interest in recent years.15 The nerve-gas-mimics diethyl cyano-
phosphonate (DCNP), diethyl chlorophosphate (DCP) and dii-
sopropyl uorophosphate (DFP) are normally used in such
studies as they are the compounds that show the same reactivity
as the real nerve agents, that is, Sarin, Soman and Tabun, but
lack the severe toxicity.
aDepartment of Chemistry, Indian Institute of Engineering Science and Technology,
Shibpur, Howrah-711 103, India. E-mail: spgoswamical@yahoo.com; Fax: +91 33
2668 2916; +91 33 2668 2961-3
bX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM,
Penang, Malaysia
cDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud,
University, Riyadh 11451, Saudi Arabia
† Electronic supplementary information (ESI) available: Experimental,
spectroscopic details and crystallographic analysis. CCDC 1415425. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c5ra24392k
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Fig. 1 The structures of nerve agents and their mimics.
Fig. 2 UV-vis absorption spectra of BSNA in CH3CN–H2O (5/5, v/v) at
pH 7.4 by using 10 mM HEPES buffer solution upon titration with 4.0
equiv. of TBAF. Inset: the naked eye color change of BSNA solution on
addition of TBAF.
The close reactivity is related with the presence of “similar”
leaving groups (i.e. F, Cl and CN) in DFP, DCP and DCNP to
those found in Sarin, Soman and Tabun (i.e. F and CN). More-
over DFP, DCP and DCNP are less toxic and in fact are not viable
nerve agents because are readily hydrolysed (poorly persistent)
when compared with Sarin, Soman and Tabun. Herein, we
report a specic chemodosimeter molecule for the differentia-
tion DCNP (tabun mimic) from other nerve agent mimics as
well as the strong electrophiles. The main observable structural
difference among DCNP (tabun mimic) and other nerve agents
or their mimics is the electrophilic phosphorous centre is
bonded to cyanide anion which is more reactive nucleophile to
attack any nucleophilic centres. Whereas in case of other nerve
agents, the anions other than cyanide like less reactive nucle-
ophiles uoride, thiolate and chloride were bonded to electro-
philic phosphorous centre of the nerve agents (Fig. 1). Thus by
targeting both the electrophilic character of phosphorus and
nucleophilic character of cyanide anion present in tabun, we
have designed and synthesized specic colorimetric and uo-
rometric probe for DCNP which is also less toxic than its mimic
nerve gas tabun.
The intermediate silyl derivative (compound 1) was prepared
by the silyl protection of hydroxyl group of 2-hydroxy-1-
naphthaldehyde
with
tert-butyldimethylsilyl
chloride
(TBDMSCl) by using a catalytic amount of imidazole in dry
CH2Cl2. The targeted compound BSNA [(E)-2-(benzothiazol-2-yl)-
3-(2-(tert-butyldimethyl-silyloxy)naphthalene-1-yl) acrylonitrile]
was prepared by the condensation reaction of compound 1 with
2-benzothiazole acetonitrile using two drops of piperidine in dry
ethanol (Scheme 1).
To use BSNA as a chemosensor for the sequential sensing of Fꢀ
and DCNP in a relay manner, at rst the selectivity of the sensor
towards Fꢀ is studied in CH3CN : H2O (v/v, 5 : 5) at pH 7.4 by UV-
vis and uorescence spectra. The UV-vis spectrum of BSNA shows
moderately strong absorption band at 320 nm and 385 nm.
The absorption study of BSNA solution (c ¼ 2 ꢁ 10ꢀ5 M) is
carried out with Fꢀ ion, the addition of gradually increasing
concentrations of uoride (as its tetrabutylammonium salt)
resulted the decrease of the absorption peak at 320 nm and
increase of the absorption peak at 410 nm with an isosbestic
point at 335 nm in dramatic color development from colorless
to pale green (Fig. 2).
Results and discussions
The BSNA shows a weak emission band at 486 nm in aceto-
nitrile/H2O (5/5, v/v, 25 ꢂC) at pH 7.4 by using 10 mM HEPES
buffer solution in the absence of Fꢀ. However, aer addition of
Fꢀ, it immediately exhibits green uorescence which results the
increase of 12 fold emission intensity at the same wavelength
(486 nm) through a specic cyclization reaction triggered by the
strong affinity of uoride toward silicon by the formation of
Here we have proposed a relay recognition strategy in a single
platform as a new pathway by using two analytes (Fꢀ and DCNP)
in a single uorescent probe BSNA and here we disclose anion
(Fꢀ) to nerve gas relay recognition by using sequential chemo-
dosimetric approaches which demonstrate signicant
improvement of uorescence in different channel by uoride
induced desilylation followed by the use of iminocoumarin (as
a DCNP signalling site) – benzothiazole in naphthol backbone.
Fig. 3 (a) Fluorescence spectra of the receptor BSNA with TBAF in
Scheme 1 Reagents and conditions: (a) tert-butyldimethylsilyl chlo- CH3CN/H2O (5/5, v/v, 25 ꢂC) at pH 7.4 by using 10 mM HEPES buffer
ride, imidazole, dry DCM, 0 ꢂC, 8 h, under N2. (b) 2-Benzothiazole solution. (b) Change of emission intensity in BSNA after addition of
acetonitrile, 2–3 drops piperidine, dry EtOH, r.t.
each of the guest anions (c ¼ 2 ꢁ 10ꢀ4 M).
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Fig. 4 (a) Fluorescence spectra of in situ system generated BBCI
(BSNA + Fꢀ) (c ¼ 2 ꢁ 10ꢀ5 M) with DCNP in CH3CN/H2O (5/5, v/v, 25
ꢂC) at pH 7.4 by using 10 mM HEPES buffer solution. (b) Fluorescence
spectra of in situ generated BBCI (BSNA + Fꢀ) with DCNP, DCP and
other interfering analytes in CH3CN/H2O (5/5, v/v, 25 ꢂC) at pH 7.4 by
using 10 mM HEPES buffer solution (c ¼ 2 ꢁ 10ꢀ4 M).
addition of DCP to the BBCI solution, the imino-coumarin
proton signal vanishes for the formation of phosphoramide
linkage and the proton signals arise at d 3.2 ppm and d 1.4 ppm
for –CH2– and –CH3– group respectively (Fig. S5†).
The addition of DCNP to the solution of BBCI solution does
not change signicantly in the absorption spectra of the solu-
tion (Fig. 5a). The uoride induced de-silylated uorescent
cyclic product BBCI is also isolated, puried and characterized
by single X-ray crystal study. The uorescence spectra of BBCI
and the increase of its emission intensity by addition of DCNP is
also identical with the in situ generated BBCI (Fig. 5b) and the
silyl bonded uoride ion does not interfere the sensing of DCNP
by in situ BBCI.
Scheme 2 The probable reaction mechanism of BSNA with Fꢀ and
BBCI with DCNP.
uorescent compound BBCI [2-(benzothiazol-2-yl)-3H-benzo-
chromen-3-imine] (Fig. 3, Scheme 2). But the addition of othꢀer
analytes (such as Clꢀ, Brꢀ, Iꢀ, NO3ꢀ, NO2ꢀ, AcOꢀ, SCNꢀ, N3
,
It is revealed that the green uorescence of BSNA solution
can be detected by using minimum 2.84 mM of Fꢀ in uores-
cence spectra and 3.09 mM of DCNP detects the bluish white
uorescence of BBCI solution (Fig. S1†). The uoride induced
de-silylation rate constant of BSNA (K) ¼ 2.01 ꢁ 10ꢀ2 sꢀ1 and
the changes of emission at different time intervals by addition
of DCNP to the BBCI solution, at xed wavelength at 480 nm by
using rst order rate equation, the rate constant (K) is found to
be 1.4 ꢁ 10ꢀ2 sꢀ1. The probe BSNA itself exhibited negligible
uorescence corresponding to a peak of weak emission inten-
sity at 486 nm on excitation at 380 nm having low uorescence
quantum yield (F ¼ 0.001). The quantum yield of new emission
band at 486 nm was 0.158 (increase of 158 fold) upon addition
of Fꢀ to the BSNA solution and 0.256 for DCNP to the BBCI
DHP, ATP, CNꢀ, HSO4ꢀ, SO32ꢀ, DCP, DCNP) to BSNA solution
does not show any response to break the oxygen–silyl bond and
also to create any observable uorescence (Fig. 3b). On the other
hand, if we add DCNP to in situ system generated BBCI by the
reaction of BSNA with Fꢀ, a large increase of emission intensity (8
fold) occurs intensifying the emission color intensity by changing
the green uorescence to bluish white by the appearance of an
emission peak at 480 nm (Scheme 3). The other analytes remain
innocent to the in situ generated BBCI solution except DCP
(Fig. 4).
The probable initial attack of the lone pair of imino nitrogen
(assisted also by conjugated lone pair on oxygen of iminocou-
marin) of BBCI takes place to DCNP releasing the CNꢀ ion
which attacks the double bond of imino-coumarin moiety and
the resulting ICT via resonance from imino-coumarin ring to
benzothiazole nitrogen forms a six-membered cyclic product
(BBCI–DCNP).
The cyclization induced uorescence enhancement (CIFE) is
also responsible for the generation of bluish-white uores-
cence. In case of DCP the initial attack by the lone pairs of
nitrogen of acidic –NH of BBCI to DCP creates slight uores-
cence enhancement but due to the absence of any leaving
nucleophilic group like CNꢀ in DCNP (released Clꢀ from DCP is
less nucleophilic rather than CNꢀ from DCNP), the probability
of formation of cyclic product is almost nil which differs DCNP
Fig. 5 (a) Comparison of absorption spectra of BSNA, BBCI and BBCI
+ DCNP in CH3CN/H2O (5/5, v/v, 25 ꢂC) at pH 7.4 by using 10 mM
here from DCP by using our interesting chemodosimetric probe HEPES buffer solution. (b) Fluorescence spectra of isolated de-silyla-
BSNA (Scheme 2). As indicated in the 1H-NMR spectra, aer
tion product of BSNA with TBAF (BBCI) with DCNP in CH3CN/H2O (5/
5, v/v, 25 ꢂC) at pH 7.4 by using 10 mM HEPES buffer solution.
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Fig. 6 Upper panel: The fluorescence changes in the solid phase.
Lower panel: The naked eye color change in the ambient light in the
solid phase.
Fig. 8 Comparison of partial 1H-NMR spectra of (a) BSNA; (b) BBCI; (c)
BBCI + DCNP in CDCl3.
coumarin moiety (BBCI) in which the Ha proton shied to
higher region at d 9.77 ppm due to deshielding effect by the
strong electron withdrawing effect of cyanide and benzothiazole
ring and a new peak appears at d 3.75 ppm corresponding to
–NH proton signal (Hb). On addition of DCNP to BBCI solution,
due to high acidic property of –NH proton, it attacks DCNP to
make free cyanide ion which further attacks the double bond of
imino coumarin moiety which results diminishing of –NH
proton signal and the shiing of Ha proton in higher eld at
d 5.37 ppm due to cyanide attack.
The reaction of BBCI with DCNP was also examined by the
treatment of BBCI with DCNP and subjecting the reaction
solution to ESI-MS analysis. The 1H-NMR spectra (Fig. S10†) and
a major peak located at 445.0569 was identied (Fig. S11†),
which is consistent with the theoretical exact mass of the BBCI–
DCNP complex (C23H16N3O3PS+; 445.065), conrming the
formation of the compound in the assay system. Thus by the 1H-
NMR, HRMS and X-ray crystallography, the probable mecha-
nism for the sensing of Fꢀ and DCNP in a single platform
(BSNA) in a relay manner can be explained (Scheme 3).
The silyl-protected BSNA at rst reacts with uoride and
uoride induced desilylation of the –OTBDMS group of BSNA
forms a uorescent compound iminocoumarin in naphthol
backbone which is responsible for the generation of green
uorescence at 486 nm. Then aer addition of DCNP to the
BSNA + Fꢀ solution, the reactive imino nitrogen reacts with
DCNP to release CNꢀ which reacts with the double bond of
iminocoumarin ring (BBCI) to form the cyclic product (BBCI–
DCNP) and increases the uorescence at 480 nm (green uo-
rescence turns to slight bluish white) (Scheme 3).
solution corresponding to blue-shied emission peak at 480 nm
(increase of 256 fold). For the handy application of the sensing,
dip-stick method is very much useful. In this method, the
emission color change in the test strips was identied by
immersing the TLC plate to the BSNA, BBCI and BBCI + DCNP
solutions followed by evaporating the solvent to dryness. The
emission and naked eye color change were observed on the
plate from colorless to different colors (Fig. 6).
This type of dipstick method is very much helpful for the
instant qualitative information without remedying any type of
time consuming instrumental analysis. The competition
experiment was also carried out by adding uoride and DCNP to
the solution of BSNA and BBCI respectively in the presence of
commonly employed interfering analytes.
The selectivity prole diagram (Fig. 7) reveals that uoride
induced uorescence enhancement remains almost unper-
turbed by the coexistence of other interfering analytes which
remain innocent toward sensing of uoride. The DCNP induced
uorescence enhancement also remains undisturbed in pres-
ence of different analytes except slight interference by DCP.
In the comparison of 1H-NMR spectra (Fig. 8; Scheme 3), we
have seen that the Ha proton of BSNA shows a sharp peak at
d 8.71 ppm. But aer addition of TBAF to BSNA solution the
uoride induced desilylation renders to the formation of imino-
Fig. 7 Fluoride and DCNP selectivity profile of the sensor BSNA and
BBCI respectively: (a) (red bars) change of fluorescence of BSNA + 10.0
equiv. of different analytes; (turquoise bars) change of fluorescence of
sensor + 10.0 equiv. of different analytes, followed by 10.0 equiv. Fꢀ at
486 nm. (b) (red bars) Change of emission intensity of BBCI + 10.0
equiv. of different analytes; (turquoise bars) change of emission Scheme 3 Anion to nerve gas relay in iminocoumarin benzothiazole
intensity of sensor + 8.0 equiv. of different analytes, followed by 8.0 platform in 2-hydroxy-1-naphthaldehyde backbone by “off–on–on”
equiv. DCNP at 480 nm.
phenomenon.
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CH3CN : H2O (v/v, 5 : 5) at pH-7.4 by using 10 mM HEPES buffer
solution. Solutions of various concentrations containing sensor
and increasing concentrations of different analytes were
prepared separately. The spectra of these solutions were recor-
ded by means of UV-vis methods.
By uorescence method. For uorescence titrations, stock
solution of the sensor (c ¼ 2 ꢁ 10ꢀ5 M) was prepared for the
titration of different analytes in CH3CN : H2O (v/v, 5 : 5) at pH-
7.4 by using 10 mM HEPES buffer solution. The solution of the
different guests like Fꢀ, Clꢀ, Brꢀ, Iꢀ, NO3ꢀ, NO2ꢀ, AcOꢀ, SCNꢀ,
N3ꢀ, DHP, ATP, CNꢀ, HSO4ꢀ, SO32ꢀ, DCP, DCNP were also
prepared in the order of (c ¼ 2 ꢁ 10ꢀ4 M). Solutions of various
concentrations containing sensor and increasing concentra-
tions of different ions were prepared separately. The spectra of
these solutions were recorded by means of uorescence
methods.
Fig. 9 The molecular structure of the BBCI, showing 50% probability
displacement ellipsoids for non-H atoms and the atom-numbering
scheme.
In the X-ray crystallographic studies of BBCI (Fig. 9), the 3H-
benzo[f]chromene ring system, is almost planar, with a r.m.s.
ꢂ
˚
deviation of 0.067 A, and makes a dihedral angle of 7.60(6) with
the benzo[d]thiazole ring system. In the crystal, no intermo-
lecular hydrogen bonds are observed. The molecules are
stacked along the a-axis and are consolidated by weak p–p
interactions involving the thiazole/benzene (C10/C11/C16–C19)
and thiazole/2H-pyran rings [centroid–centroid distances of
Determination of uorescence quantum yield. Here, the
quantum yield f was measured by using the following equation,
2
fx ¼ fs(Fx/Fs)(As/Ax)(nx /ns2)
˚
3.6641(13) and 3.6849(12) A, respectively].
where, x & s indicate the unknown and standard solution
respectively, f ¼ quantum yield, F ¼ area under the emission
curve, A ¼ absorbance at the excitation wave length, n ¼ index of
refraction of the solvent. Here f measurements were performed
using anthracene in ethanol as standard [f ¼ 0.27] (error
ꢃ10%).
Conclusion
In conclusion here an unprecedented relay recognition of anion
Fꢀ and nerve agent simulant DCNP has been achieved and
further demonstrated for the selectivity of DCNP over DCP by
colorimetric and uorimetric pathway. The in situ system
generated BBCI from the sensing of Fꢀ to the system BSNA and
also the isolated product BBCI showed good relay recognition
ability for DCNP via the formation of a six-member cyclic
product (BBCI–DCNP) which is also responsible for the gener-
ation of uorescence in different channel. For practical appli-
cation, the dipstick method by using different test strips on the
sensors is very much helpful for the instant qualitative infor-
mation without remedying any type of time consuming instru-
mental analysis for the detection of Fꢀ as well as DCNP.
Experimental
Synthesis of 2-hydroxy-1-napthylaldehyde
2-Hydroxy-1-napthylaldehyde was synthesized by the reported
procedure.16 b-Naphthol (1 g, 0.0069 mol) was placed in a 100
mL r.b. ask tted with a reux condenser, a magnetic stirrer
and a dropping funnel. It was then dissolved in EtOH at 80–90
ꢂC. NaOH (2 g, 0.05 mol) in 20 mL water was then added
dropwise to this hot solution when the solution became darker.
Aer half an hour, CHCl3 (1.3 g, 0.011 mol) was added dropwise
using a dropping funnel. Development of deep blue coloration
indicates the reaction has started. Near the end point of the
addition, the sodium salt of the phenolic aldehyde was sepa-
rated out. The reaction mixture was stirred for six hours. Excess
ethanol and chloroform were distilled off. The dark oil le was
mixed with a considerable amount of sodium chloride. Suffi-
cient water was added to dissolve the salt, and the oil was
separated and washed with hot water. Then, the solution was
neutralized with dilute hydrochloric acid and extracted with
chloroform. Finally, the product was puried by 60–120 silica
gel by 1–2% ethyl acetate in pet ether. Yield of the product was
General
Unless otherwise mentioned, chemicals and solvents were
purchased from Sigma-Aldrich chemicals Private Limited and
were used without further purication. Melting points were
determined on a hot-plate melting point apparatus in an open-
mouth capillary and are uncorrected. 1H-NMR spectra were
recorded on Brucker 300 MHz instrument. For NMR spectra,
CDCl3 was used as solvent using TMS as an internal standard.
Chemical shis are expressed in d units and H-1H and H-C
coupling constants in Hz. UV-vis titration experiments were
performed on a JASCO UV-V530 spectrophotometer and uo-
rescence experiment was done using PerkinElmer LS 55 uo-
rescence spectrophotometer using a uorescence cell of 10 mm
path.
1
1
ꢂ
500 mg (50%). Melting point: 79–80 C.
Synthesis of BSNA
2-Hydroxy-1-napthylaldehyde (300 mg, 1.74 mmol) was dis-
solved in dry dichloromethane under nitrogen atmosphere at
0 ꢂC. Than catalytic amount imidazole (70 mg, 1.02 mmol) was
General method of UV-vis and uorescence titration
By UV-vis method. For UV-vis titrations, stock solution of the added to it and stirred for half an hour. Tetrabutyl dimethyl silyl
sensor was prepared (c ¼ 2 ꢁ 10ꢀ5 M) in was studied in chloride (262 mg, 1.74 mmol) was added slowly to the reaction
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mixture and a white precipitation is separated out. The whole
mixture was stirred at room temperature for 3 h. Aer
completion of the reaction, water was added and the compound
was extracted with dichloromethane. The volume of organic
solvent was reduced under high pressure and the crude gummy
product (compound 1) was directly used to the next step without
purication by column chromatography due to its high insta-
bility. The compound 1 was dissolved in dry ethanol under
nitrogen atmosphere. Aer stirring for few minutes, 2-benzo-
thiazole acetonitrile (200 mg, 1.15 mmol) and 2–3 drops
piperidine were added to the reaction mixture. Aer completion
the reaction monitored by TLC, the target product BSNA was
puried by column chromatography using 10% ethyl acetate in
pet ether (v/v). Yield-500 mg, 65%.
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ꢂ
Mp. 120–130 C.
1H NMR (CDCl3, 300 MHz): d (ppm): 8.71 (s, 1H), 8.11 (m,
1H), 7.95 (m, 1H), 7.92 (m, 1H), 7.83 (d, 2H, J ¼ 1.2 Hz), 7.67 (d,
2H, J ¼ 7.8 Hz), 7.56 (m, 1H), 7.41 (m, 1H), 7.14 (d, 1H, J ¼ 6.3
Hz), 1.65 (s, 3H), 1.02 (s, 9H), 0.26 (s, 3H).
HRMS (ESI-TOF): (m/z, %): M + calculated for C26H26N2OSSi
is 442.1535; found: 443.1609 (M + H)+; (M + Na)+ calculated
465.1433; found: 465.1389.
Elemental analysis: calculated value: C, 70.55; H, 5.92; N,
6.33; observed value: C, 70.51; H, 5.94; N, 6.35.
5 (a) K. L. Kirk, Biochemistry of the Halogens and Inorganic
Halides, Plenum Press, New York, 1991, p. 58; (b)
H. S. J. Horowitz, Public Health Dent, 2003, 63, 3–8.
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Amsterdam, 1984, pp. 366–393; (b) J. R. Farley, J. E. Wergedal
and D. J. Baylink, Science, 1983, 222, 330–332; (c)
M. Kleerekoper, Endocrinol. Metab. Clin. North Am., 1998,
27, 441–452.
Synthesis of BBCI
To a stirred solution of BSNA (300 mg, 0.68 mmol) in CH3CN (10
mL) was added tetrabutylammonium uoride (180 mg, 0.68
mmol) at room temperature. The mixture was stirred for 3 h,
and the solvent was evaporated under reduced pressure. The
resulting crude residue was puried by ash column chroma-
tography (10 : 1 / 1 : 1) on silica gel to afford BBCI as an
orange solid (150 mg, 67%).
7 (a) R. Hu, J. Feng, D. Hu, S. Wang, S. Li, Y. Li and G. Yang,
Angew. Chem., Int. Ed., 2010, 49, 4915–4918; (b) S. Y. Kim
and J. I. Hong, Org. Lett., 2007, 9, 3109–3112; (c)
O. A. Bozdemir, F. Sozmen, O. Buyukcakir, R. Guliyev,
Y. Cakmak and E. U. Akkaya, Org. Lett., 2010, 12, 1400–
1403; (d) S. Goswami, A. K. Das, A. Manna, A. K. Maity,
H. K. Fun, C. K. Quah and P. Saha, Tetrahedron Lett., 2014,
55, 2633.
8 (a) J. J. Gooding, Anal. Chim. Acta, 2006, 559, 137; (b)
L. M. Eubanks, T. J. Dickerson and K. D. Janda, Chem. Soc.
Rev., 2007, 36, 458; (c) B. M. Smith, Chem. Soc. Rev., 2008,
37, 470; (d) M. Wheelis, Pure Appl. Chem., 2002, 74, 2247;
(e) H. H. Hill Jr and S. J. Martin, Pure Appl. Chem., 2002,
74, 2281; (f) S. Goswami, A. Manna and S. Paul, RSC Adv.,
2014, 4, 21984; (g) A. K. Mahapatra, K. Maiti, S. K. Manna,
R. Maji, S. Mondal, C. D. Mukhopadhyay, P. Sahoo and
D. Mandal, Chem. Commun., 2015, 51, 9729–9732; (h)
S. Goswami, S. Das and K. Aich, RSC Adv., 2015, 5, 28996.
9 (a) M. T. McBride, S. Gammon, M. Pitesky, T. W. O. Brien,
T. Smith, J. Aldrich, R. G. Langlois, B. Colston and
K. S. Venkateswaran, Anal. Chem., 2003, 75, 1924; (b)
A. J. Russell, J. A. Berberich, G. F. Drevon and
R. R. Koepsel, Annu. Rev. Biomed. Eng., 2003, 5, 1; (c)
H. Wang, J. Wang, D. Choi, Z. Tang, H. Wu and Y. Lin,
Biosens. Bioelectron., 2009, 24, 2377.
ꢂ
Mp. 220–230 C.
1H NMR (CDCl3, 300 MHz): d (ppm): 9.78 (s, 1H), 8.36 (d, 1H,
J ¼ 7.5 Hz), 8.13 (d, 1H, J ¼ 3.9 Hz), 8.04 (m, 2H), 7.83 (d, 2H, J ¼
8.1 Hz), 7.77 (m, 1H), 7.65 (m, 1H), 7.54 (m, 1H), 7.48 (m, 1H),
3.76 (s, 1H).
HRMS (ESI-TOF): (m/z, %): M + calculated for C20H12N2OS is
328.067; found: 329.0745 (M + H)+.
Elemental analysis: calculated value: C, 73.15; H, 3.68; N,
8.53; observed value: C, 74.18; H, 3.66; N, 8.52.
Acknowledgements
Authors thank the DST and CSIR (Govt. of India) for nancial
support. A. K. D. acknowledges the CSIR for providing
fellowships.
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