Fluorescent and colorimetric detection of acid vapors by using solid-supported rhodamine hydrazides

Article abstract of DOI:10.1016/j.tetlet.2009.02.087

Rhodamine hydrazide-based chemosensors that can detect volatile acidic gases in solid state have been developed. The rhodamine hydrazide probes adsorbed on filter paper respond fluorescently and colorimetrically only to volatile acidic gases but not to organic bases nor to other volatile organic compounds (VOCs). Diethyl chlorophosphate (DCP), one of model compounds used for the studies of Chemical Warfare Agent (CWA), could also be detected by using this method.

Full text of DOI:10.1016/j.tetlet.2009.02.087

Tetrahedron Letters 50 (2009) 2010–2012
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Fluorescent and colorimetric detection of acid vapors by using
solid-supported rhodamine hydrazides
*
Shincheol Kang, Sungwook Kim, Young-Keun Yang, Shinhyo Bae, Jinsung Tae
Department of Chemistry and Center for Bioactive Molecular Hybrids (CBMH), Yonsei University, Seoul 120-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Rhodamine hydrazide-based chemosensors that can detect volatile acidic gases in solid state have been
developed. The rhodamine hydrazide probes adsorbed on filter paper respond fluorescently and colori-
metrically only to volatile acidic gases but not to organic bases nor to other volatile organic compounds
(VOCs). Diethyl chlorophosphate (DCP), one of model compounds used for the studies of Chemical War-
fare Agent (CWA), could also be detected by using this method.
Received 26 December 2008
Revised 10 February 2009
Accepted 12 February 2009
Available online 15 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
with NH2NH2 or NH2NHMe under refluxing EtOH solutions8 pro-
duced compounds 4c (75%), 4d (78%), 5b (42%), 5c (74%), 6b
The real-time sensing of volatile organic compounds (VOCs),
such as amines,1 hydrocarbons,2 explosives,3 and chemical warfare
agents,4 has been an active research area. Although much success
has been achieved for the detection of VOCs by using various opti-
cal detection methods, the fluorescent probe-based sensing of
VOCs still remains challenging, mainly because there are not many
organic materials available which are sufficiently fluorescent in so-
lid state and suitable for vapor detection.5
O
H
O
R
H+
N
N
R
R2N
O
NR2
R2N
O
NR2
Non-fluorescent
Fluorescent
Recently, rhodamine amide derivatives are widely used as fluo-
rescent probes for detection of various ions.6 While the spirocyclic
form of a rhodamine amide is non-fluorescent and colorless, the
ring-opened form is strongly fluorescent and pink colored (Scheme
1).7 This characteristic equilibrium is highly sensitive to the pH of
the solutions. In acidic solutions, the ring-opened form is predom-
inant, and therefore strongly fluorescent. Although this acid-sensi-
tive equilibrium has been well known in solutions, its properties in
solid states are not well examined. Herein, we report rhodamine
hydrazide derivatives that respond to acid vapors in solid state.
We envisioned that the H+-promoted ring-opening reaction of
rhodamine amides could be utilized to detect volatile acids. Thus,
we have prepared several rhodamine 6G (4a–e), rhodamine B
(5a–c), and fluorescein (6a–c) amide derivatives to screen probes
that are suitable for the detection of acid vapors in solid state
(Scheme 2).
Scheme 1. H+-promoted ring opening of rhodamine amides.
O
CO2Et
O
EtHN
O
NEt
Y
O
Y
Rhodamine 6G (1)
Y= NEt2, Rhodamine B base (2)
Y= OH, Fluorescein (3)
see text
for reaction
conditions
X
Y
Z
4a : Me
4b :
4c :
4d :
4e :
NHEt Me
OH
O
NH2
NHMe
Compound 4a was prepared from
1 in the presence of
N
Z
X
Y
X
Y
MeNH2ÁHCl and Et3N under refluxing EtOH solution in 88% yield.
Compound 4b was prepared from 1 in three steps: (1) NaOH,
EtOH–H2O, reflux; (2) POCl3, CH2Cl2, rt; and (3) NH2OHÁHCL, EtOH,
Et3N, reflux (34% yield for three steps). Treatments of 1, 2, and 3
NMe2
Me
NH2
NHMe
Me
NH2
5a :
5b :
5c :
6a :
6b :
6c :
H
H
NEt2
OH
O
NHMe
* Corresponding author. Tel.: +82 2 2123 2603; fax: +82 2 364 7050.
E-mail address: jstae@yonsei.ac.kr (J. Tae).
Scheme 2. Synthesis of rhodamine amide derivatives.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.087

S. Kang et al. / Tetrahedron Letters 50 (2009) 2010–2012
2011
(75%), and 6c (75%). Dimethylhydrazine derivative 4e was pre-
4a
4b
4c
4d
4e
pared from 4c in the presence of MeI in acetone at room tempera-
ture (78%). Compound 5a was prepared from 2 in two steps: (1)
POCl3, CH2Cl2, r.t. and (2) MeNH2ÁHCl, Et3N, EtOH, reflux (54% yield
for two steps). And 6a was prepared from 3 in two steps: (1) cat. c-
H2SO4, MeOH, reflux and (2) MeNH2ÁHCl, Et3N, DMF, 100 °C (25%
yield for two steps).9
Solid-adsorbed fluorescent probes were prepared by dipping a
filter paper (d = 0.6 cm) into a CH2Cl2 solution of a fluorescent com-
pound (1.0 mg of a probe in 10 mL of CH2Cl2) for 2–3 s.10 Then, the
filter paper was dried in high vacuum for 48 h in dark at room tem-
perature. Fluorescent detection of an acid vapor is conducted using a
glass chamber (volume = 100 mL, d = 5 cm) with a lid. The fluores-
cent-probe adsorbed filter paper is placed in the center of the cham-
a
a
b
b
c
c
d
d
e
e
f
f
g
g
h
h
i
i
j
j
none
4a
4b
4c
4d
4e
ber, and then a volatile acid (ꢀ5
lL) is dropped into the bottom of the
none
chamber. After 15 s, the filter paper was removed from the chamber,
and then the optical and the fluorescent images were taken.
Although rhodamine amides are known to be highly fluorescent
in acidic solutions, the solid-supported rhodamine methyl amides
4a and 5a showed no apparent color changes and very weak fluo-
rescence intensities in the presence of HCl and HNO3 vapors
(Fig. 1).11 And the fluorescein amide derivatives (6aÀc) were inert
to acid vapors as expected. Strong color and fluorescence changes
were observed for rhodamine hydrazine derivatives 4c, 4d, 5b,
and 5c. However, the solid-supported rhodamine B hydrazides
(5b and 5c) were fluorescent even in the absence of acid vapors.
Therefore, we selected rhodamine 6G hydrazide derivatives (4)
for our further studies.
The solid-supported rhodamine hydrazides 4c and 4d uniformly
displayed significant color and fluorescence intensity changes in
response of volatile acids, such as HF, HCl, HBr, and HNO3
(Fig. 2a and b). But the solid-supported rhodamine amide 4a
showed no apparent color and fluorescence changes in the pres-
ence of various volatile acids. Interestingly, the solid-supported
4c and 4d even responded to acid precursors (such as AcCl, POCl3,
SOCl2, PBr3, and acryloyl chloride), which could produce HCl or HBr
indirectly by reaction with nucleophiles. This may imply that the
nucleophilic hydrazide attacks the electrophilic acid precursors
to produce HCl or HBr, which eventually induces the ring-opening
reaction of rhodamine amide derivatives. Similarly, diethyl chloro-
phosphate (DCP), one of model compounds used for the studies of
Chemical Warfare Agent (CWA), could also be detected by using
these rhodamine 6G hydrazides (4c and 4d) in solid state (Fig. 2,
vapor e). On the other hand, volatile organic bases and other vola-
tile organic compounds (VOCs) are completely silent to the rhoda-
mine 6G hydrazides in solid state (Fig. 2c and d).
4a
4c
4d
none k
none p
l
m
n
o
4a
4c
4d
q
r
s
t
u
v
w
x
Figure 2. Responses of solid-supported 4a–e to chemical vapors (5
lL in a 100 mL
chamber). (a) Color changes and (b) Fluorescence changes in the presence of acid
vapors: a. HF; b. AcCl; c. HBr; d. POCl3; e. DCP (diethyl chlorophosphate); f. SOCl2; g.
HNO3; h. c-HCl; i. PBr3; j. H2C=CHCOCl. (c) Responses to organic bases: k. pyridine; l.
i-Pr2NEt; m. Et3N; n. t-BuNH2; o. TMEDA (tetramethylethylenediamine). (d)
Responses to other volatile organic compounds: p. PhSH; q. EtSH; r. CH2Cl2; s.
ClCH2CH2Cl; t. hexane; u. pentane; v. Et2O; w. EtOAc; x. MeOH.
tions because we were not able to observe significant fluorescence
intensity changes from 5 to 20 lL of c-HCl.
The reason for the high sensitivity of rhodamine hydrazides (4c
and 4d), unlike other simple rhodamine amides (4a and 5a), to acid
vapors in solid state could be explained by the stabilized structure
7 as shown in Scheme 3. Protonation12 of the rhodamine hydrazide
DCP
HCl
Host
5 µL
10 µL
15 µL 20 µL
Figure 3. Concentration-dependent fluorescence changes of solid-supported 4d in
the presence of DCP and HCl vapors.
We further examined the concentration-dependent fluores-
cence response of 4d to DCP and HCl in solid state (Fig. 3). As the
amounts of DCP added increased from 5 to 20
intensities increased accordingly. It seems that enough HCl vapors
are generated even at 5 L of c-HCl under the experimental condi-
lL, the fluorescence
O
O
H
l
N
NHMe
H+
N
NHMe
4a 4b 4c 4d 4e 5a 5b 5c 6a 6b 6c
EtHN
O
NHEt
EtHN
O
NHEt
4d
H
O
HNO3
HCl
N H
Me
N
none
EtHN
O
NHEt
7
Figure 1. Responses of solid-supported 4À6 to acid vapors (5
lL in a 100 mL
Fluorescent
chamber). (a) Color changes in the presence of c-HCl. (b) Fluorescence changes in
the presence of c-HCl and HNO3.
Scheme 3. Proposed structure of the protonated rhodamine hydrazide 4d.

2012
S. Kang et al. / Tetrahedron Letters 50 (2009) 2010–2012
(4d) is expected to trigger opening of the non-fluorescent spirocy-
clic form to the highly fluorescent open form 7, where the proton-
ated hydrazide could be stabilized by intramolecular hydrogen
bonding.
plate. The fluorescent images were taken using a Typhoon 9210
fluorescence scanner (observed emission at 555 nm).
Acknowledgments
In summary, we have developed rhodamine hydrazide-based
chemosensors that respond fluorescently and colorimetrically to
acid vapors. The solid-supported rhodamine hydrazide probes are
highly sensitive only to volatile acids, but not to organic bases
nor to other volatile organic compounds. Diethyl chlorophosphate
(DCP), one of model compounds used for the studies of chemical
warfare agent (CWA), could also be detected by using this method.
This work was supported by KOSEF (R01-2008-000-10245-0)
and CBMH (MOST/KOSEF).
Supplementary data
Experimental procedures for the synthesis, spectral data, of new
compounds data are available. Supplementary data associated with
this article can be found, in the online version, at doi:10.1016/
j.tetlet.2009.02.087.
2. Experimental procedures
2.1. General procedure for the synthesis of rhodamine
hydrazide 4d
References and notes
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To a solution of rhodamine 6G (2.00 g, 4.18 mmol) in ethanol
(4 mL) was added methylhydrazine (1.00 mL, 19.0 mmol). The
solution was refluxed for 12 h, concentrated, and the residue was
purified by column chromatography (hexanes/ethyl acetate = 1:2)
to give 1.44 g of 4d (78%) as a white solid.
Spectral data for 4: mp decomposed at 254 °C; 1H NMR (400 MHz,
CDCl3) d 7.92À7.94 (dd, J = 5.6 Hz, 3,2 Hz, 1 H), 7.45À7.48 (m, 2 H),
7.05À7.08 (dd, J = 5.6 Hz, 3.2 Hz, 1 H), 6.38 (s, 2 H), 6.25 (s, 2 H),
4.22 (br s, 1 H), 3.48 (br s, 2 H), 3.18À3.23 (q, J = 7.0 Hz, 4 H), 2.34
(s, 3 H), 1.90 (s, 6 H), 1.30–1.33 (t, J = 7.0 Hz, 6 H); 13C NMR
(100 MHz, CDCl3) d 166.44, 152.25, 151.88, 147.45, 132.77, 130.52,
128.41, 128.22, 124.07, 122.88, 117.70, 106.39, 96.92, 65.51, 38.53,
38.50, 16.86, 14.91; IR (film, cmÀ1) 3826, 1688, 1618, 1519, 1444,
1357, 1258, 1204, 1146, 1005; HRMS m/z calcd for C27H30N4O2 (M
+ H)+ 443.2447; found 443.2455.
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(b) Langhals, H.; Krotz, O.; Polborn, K.; Mayer, P. Angew. Chem., Int. Ed. 2005, 16,
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2.2. General procedure for the fluorescent detection of acid
vapors using solid-supported rhodamine hydrazide
York, 2001. Chapter 10.
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10. Using high concentrations of fluorescent materials or dipping longer time often
resulted in colored filter papers.
11. In CH2Cl2 solutions, similarly, while 4a induced very weak fluorescence
intensity changes in the presence of HCl and DCP, the rhodamine hydrazide 4d
showed strong fluorescent responses under the same conditions (see
Supplementary data).
Filter papers (Advantec, 0.6 cm in diameter) were dipped in the
CH2Cl2 (10 mL) solution of a rhodamine hydrazide (1.0 mg) for 2–
3 s each. Then, the collected filter papers were dried in high vac-
uum for 48 h in dark at room temperature. The fluorescent-probe
adsorbed filter paper is placed in the center of a glass chamber
(volume = 100 mL, d = 5 cm). Then, a drop of volatile acid (ꢀ5
lL)
12. The hydrazides of carboxylic acids are known to undergo protonation at the b-
nitrogen atom in acidic media: Comprehensive Organic Chemistry; Barton, D.,
Ollis, W. D., Eds.; Oxford: Pergamon, 1979.
is dropped into the bottom of the chamber using a micro–syringe,
and the chamber was covered for 15 s. The filter paper was re-
moved from the chamber and placed in a well of a 96-well assay