Acridinedione as selective flouride ion chemosensor: A detailed spectroscopic and quantum mechanical investigation

Article abstract of DOI:10.1039/c7ra11974g

The use of small molecules as chemosensors for ion detection is rapidly gaining popularity by virtue of the advantages it offers over traditional ion sensing methods. Herein we have synthesized a series of acridine(1,8)diones (7a-7l) and explored them for

Full text of DOI:10.1039/c7ra11974g

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Acridinedione as selective flouride ion
chemosensor: a detailed spectroscopic and
Cite this: RSC Adv., 2018, 8, 1993
quantum mechanical investigation†
b
Nafees Iqbal,a Syed Abid Ali,a Iqra Munir,a Saima Khan,b Khurshid Ayub,
c
ef
Mariya al-Rashida,
and Abdul Hameed
Muhammad Islam,d Zahid Shafiq,dg Ralf Ludwig
a
*
The use of small molecules as chemosensors for ion detection is rapidly gaining popularity by virtue of the
advantages it offers over traditional ion sensing methods. Herein we have synthesized a series of
acridine(1,8)diones (7a–7l) and explored them for their potential to act as chemosensors for the
detection of various anions such as fluoride (Fꢀ), acetate (OAcꢀ), bromide (Brꢀ), iodide (Iꢀ), bisulfate
(HSO4ꢀ), chlorate (ClO3ꢀ), perchlorate (ClO4ꢀ), cyanide (CNꢀ), and thiocyanate (SCNꢀ). Acridinediones
were found to be highly selective chemosensors for fluoride ions only. To investigate in detail the
mechanism of selective fluoride ion sensing, detailed spectroscopic studies were carried out using UV-
visible, fluorescence and 1H NMR spectroscopy. Fluoride mediated (NH) proton abstraction of
acridinedione was found to be responsible for the observed selective fluoride ion sensing. Quantum
mechanical computational studies, using time dependent density functional theory (TDDFT) were also
carried out, whereupon comparison of acridinedione interaction with fluoride and acetate ions explained
the acridinedione selectivity for the detection of fluoride anions. Our results provide ample evidence and
rationale for further modulation and exploration of acridinediones as non-invasive chemosensors for
fluoride ion detection in a variety of sample types.
Received 31st October 2017
Accepted 26th December 2017
DOI: 10.1039/c7ra11974g
rsc.li/rsc-advances
tailored or “custom-made” to make them more suitable for
specic applications, for example such molecules can be easily
1. Introduction
made more or less water soluble or membrane permeable. The
use of chemosensors offers non-invasive and non-destructive
methods of ion analysis; these are particularly desirable traits
for ion sensing in biological samples such as cells and tissues.
The mechanism of ion sensing by these chemosensors usually
involves a modulation of some measurable property (such as
absorbance or uorescence) of the chemosensor (receptor or
ligand), upon binding with ions. Anion detection with small
molecules generally occurs via addition of anions to the
receptor,2,3 or removal of acidic protons from the receptor
resulting in visible colorimetric changes.4,5
A range of different compounds such as acridinium,2 qui-
nolone,6 and urea/thiourea-based7 receptors have been reported
as chemosensors in anion detection via addition, substitution,
or photo-induced electron transfer mechanisms.1 Ion detection
for anions such as halides (Fꢀ, Clꢀ, Brꢀ, Iꢀ), acetate (OAcꢀ),
sulfate, chlorate, cyanide and thiocyanate carries much analyt-
ical importance. Among the pool of anions, uoride detection
possesses signicant importance in osteoporosis, which is
characterized by uoride accumulation in bones.8 In recent
years, selective uoride detection has received considerable
attention due to its consumption in variety of products such as
toothpastes, pesticides, fertilizers etc. Compounds bearing
In the realm of sensors, the application of small molecules as
chemosensors has emerged as an exciting area of research with
vast and diverse applications in the areas of biological, envi-
ronmental, clinical and industrial research.1 A variety of small
molecules have found applications as ion sensors, where both
cations and anions can be precisely and selectively determined.
Moreover, the structure of these small molecules can be easily
aH. E. J. Research Institute of Chemistry, International Center for Chemical and
Biological Sciences, University of Karachi, Karachi-75270, Pakistan. E-mail:
abdul_hameed8@hotmail.com; abdul_hameed@iccs.edu; Fax: +92-21-3481901; Tel:
+92-21-99261701-2
bDepartment of Chemistry, COMSATS Institute of Information Technology,
Abbottabad, KPK, Pakistan 22060
cDepartment of Chemistry, Forman Christian College,
Ferozepur Road, Lahore, Pakistan
A Chartered University,
dInstitute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan
e
¨
¨
Leibniz-Institut fur Katalyse e. V. an der Universitat Rostock, Albert-Einstein-Str. 29a,
18059 Rostock, Germany
fDepartment of Physical Chemistry, University of Rostock, Dr.-Lorenz-Weg 1, 18059
Rostock, Germany
gDepartment of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
† Electronic supplementary information (ESI) available: Supplementary
information contains the NMR spectra of the synthesized compounds. See DOI:
10.1039/c7ra11974g
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amino or hydroxyl groups have been known to act as chemo- are also known as highly effective chemosensors for metal
sensors for uoride detection either via deprotonation of acidic ions.27 Similarly acridinedione-based heteroditopic hosts con-
protons, or via hydrogen bond formation with uoride.1,9 taining oxyethylene linkages have been used for metal ion
Previously rhodamine based molecules were found to act as detection as well as for uoride ion detection.28 Acridinedione
selective sensors for uoride ions, moreover they were also functionalized with thiourea moiety was found to be non-
successfully applied for imaging of uoride content in live selective anion sensor via PET (Photoinduced Electron Trans-
cells.10 Similarly receptors containing thiosemicarbazide moie- fer) mechanism.29 In continuation of our work on development
ties also act as ion-sensors towards different anions. In this of novel anion chemosensors3 we decided to synthesize a series
case, the acidic protons of thiosemicarbazide moiety act as of 9-phenyl-acridine-1,8-diones and explore their potential as
binding sites and can selectively bind uoride ions.11,12 Related anion chemosensors Fig. 1.
to this class of sensors, azo dye-semicarbazones have also been
known to act as anion sensors via related mechanism.13 N-
2. Results and discussion
2.1. Chemistry
Monoalkylated
1,4-diketo-3,6-diphenylpyrrolo[3,4-c]-pyrroles
have been developed as efficient and highly selective uores-
cent probes for uoride ions14 Recently naphthodipyrrolidones
were found to act as sensitive and selective probes for uoride
ions.15 In the present study, we explored phenyl acridine(1,8)
diones as chemosensors for a range of different anions and
found them to be selective only for uoride detection.
The synthesis of a series of 9-phenyl-acridine-1,8-diones (7a–7l)
was carried out under solvent-free conditions using newly
synthesized novel morpholinium-based ionic liquids (3–6), that
were also synthesized in our lab. Ionic liquids (ILs) serve as an
excellent alternative for traditionally volatile organic solvents.
In contrast to typically obnoxious organic solvents, ILs provide
alternative eco-friendly, green method of syntheses.30,31 Among
the pool of ionic liquids, imidazole or pyridine-based ionic
liquids have been employed as catalysts in organic reactions,
however the inert nature of imidazole, and high toxicity and
volatility of pyridine are major obstacles.32–34 N-Alkyl morpho-
line, being a less toxic compound, provides an easy access to
inexpensive morpholinium cation for ionic liquid preparation
(Fig. 2). Although morpholine as a base has been diversely
employed in organic reactions, the use of N-alkylated
morpholinium-based ionic liquids has been less exploited in
organic synthesis.
Acridine(1,8)diones are a well-known class of compounds
and have found many interesting applications. They exhibit
excellent photo-physical properties,16 making them ideal
candidates to be used as laser dyes.17 Acridine(1,8)diones are
used as photosensitizers18 and as photoinitiators in polymeri-
sation reactions.19 These molecules can exist in neutral,
protonated and a deprotonated forms.20 Phenyl acridine(1,8)
dione contains a 1,4-dihydropyridine scaffold in the center of
the molecule. 1,4-Dihydropyridine (DHP) belongs to a well-
known class of compounds with signicant biological
activity21 such as antitumor,22 antitubercular activity,23 antihy-
pertensive,24 and anti-inammatory activity.25 Previously acri-
dine(1,8)dione derivatives have been used for metal ion sensing,
for example aza-crown ether acridinedione-functionalized
quantum dots and aza-crown ether acridinedione-
functionalized gold nanorods have been used to detect Ca2+
and Mg2+ ions.26 Other molecules such as dibutylaniline- and/or
pyridine-containing 2,6,9,10-tetrarylvinylanthracene cruciforms
Synthesis of morpholinium-based ionic liquids (ILs) is given
in Scheme 1. The N-alkyl (Me, Et) morpholine was treated with
corresponding alkyl bromides (C5 and C7) in toluene at 118–
120 ꢁC until the complete consumption of starting materials as
monitored by TLC. In the next step, the counter anion (Brꢀ) was
exchanged with uoride (Fꢀ) by using silver uoride, since
Fig. 1 Structures of some reported molecules as selective probes/chemosensors for fluoride ion.
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These newly synthesized morpholinium-based ionic liquids
(3–6) were employed as reaction media and catalyst under
solvent-free conditions for the synthesis of 9-phenyl-acridine-
1,8-diones (7a–7l). One-pot multicomponent reaction between
dimidone (2 equiv.), benzaldehyde (1 equiv.) and ammonium
acetate (1 equiv.) was successfully carried out using
morpholinium-based ionic liquids (3–6) as catalysts (1.0 equiv.)
ꢁ
at 115–120 C. Synthesis of one of the acridinedione derivative
(7f) was carried out under these above optimized conditions
using different ILs (3–6), the percentage yields of product (7f)
obtained with these different ILs were compared, and were not
found to be very different from one another (Table 1). In order to
signify the catalytic efficiency of morpholinium-based ionic
liquids in reactions demanding high temperatures, thermal
studies of IL 3 (as model IL) were studied in detail using
differential scanning calorimetry (DSC), thermogravimetric
analysis (TGA), and derivative thermogravimetry (DTG) (data
given in Fig. S5a and b†).
Fig. 2 Structures of imidazolium, pyridinium, TBAF and morpholi-
nium-based ILs.
2.2. Anion sensing study
Anion sensing by small molecules as chemosensors is a rapidly
growing area of research. Among the anions of biological
signicance, uoride occupies a unique place due to its utili-
zation in dental care creams and over-accumulation in bones,
which leads to osteoporosis. Accordingly, we investigated the
potential of acridinediones in anion sensing for the possible
detection of uoride (Fꢀ), acetate (OAcꢀ), bromide (Brꢀ), iodide
(Iꢀ), bisulfate (HSO4ꢀ), chlorate (ClO3ꢀ), perchlorate (ClO4ꢀ),
cyanide (CNꢀ), and thiocyanate (SCNꢀ) ions, by using naked
eye, UV-visible, uorescence and NMR spectroscopic tech-
niques. In this study, the acridinediones 7i and 7l were selected
as model compounds to act as chemosensor in anion sensing
study. Stock solutions of acridinedione receptor (chemosensor)
and anions were freshly prepared in CH3CN or DMSO (in case of
KCN and KSCN) and then diluted in CH3CN for analysis. Solu-
tions of receptors 7i and 7l were treated with different anions
Fꢀ, OAcꢀ, Brꢀ, Iꢀ, HSO4ꢀ, ClO3ꢀ, ClO4ꢀ, CNꢀ, and SCNꢀ, and
were observed for any change in color with naked eye, and
under UV irradiation. Only addition of uoride ions caused
a conspicuous change in color of receptors 7i and 7l from
colorless to yellow, indicating that acridinediones 7i and 7l are
selective chemosensors for uoride ion detection (red line
curve). Fig. 4 (top) shows, (a) solution of 7i without any uoride
Scheme 1 Synthesis of morpholinium-based ionic fluoride liquids (3–
6). (a) Alkyl bromides, toluene, 118–120 ꢁC; (b) aqueous silver fluoride
solution.
uoride ion exhibits overlying catalytic efficiency and mild basic
characteristics in mediating organic reactions.35,36 Thus,
morpholinium-based ionic liquids with uoride counter anion
could potentially serve as better alternate to TBAF (tetrabutyl
ammonium uoride, a commercially available IL) in organic
synthesis due to easy and rapid preparation of morpholinium-
based ionic liquids from cost effective commercially available
N-alkylated morpholine Scheme 2.
Table 1 Comparison of percentage yields of acridine(1,8)dione (7f)
synthesized via one-pot multicomponent reaction using different ILs
(3–6)a
Product (7f)
Morpholinium-ILs
Equiv.
yield (%)
3
4
5
6
1.0
1.0
1.0
1.0
74
73
73
71
a
Conditions: morpholinium-ILs (1.0 equiv.), heat (115–120 ꢁC), 16–
18 h.
Scheme 2 Synthesis of 9-phenyl-acridine-1,8-diones 7a–l.
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ion as observed by naked eye, (b) solution of 7i (1 equiv.) with
added uoride ions (10 equiv.) as observed by naked eye, and (c)
same solution of 7i with added uoride ion as observed under
UV irradiation (254 nm). These observations were conrmed via
detailed UV-visible studies shown in Fig. 3a (7i) and Fig. 3b (7l),
uorescence, and 1H-NMR studies with 7i.
The UV-visible spectroscopic studies were carried out with 7i
and 7l (1 equiv.) by adding 10 equiv. of different ions (Fꢀ, OAcꢀ,
Brꢀ, Iꢀ, HSO4ꢀ, ClO3ꢀ, ClO4ꢀ, CNꢀ, and SCNꢀ) in CH3CN/
DMSO and then further diluting with CH3CN solvent. The UV
spectra of both receptors (7i and 7l) showed lmax at 370 nm
which is attributed to intermolecular charge transfer (ICT)
transition between nitrogen atom of acridine scaffold and
carbonyl group.37 Aer titration with different anions, the both
probes showed a new shi with lmax at 460 nm when titrated
against uoride anion (Fig. 4). As the anion sensing pattern of
both receptors was found to be similar, only receptor 7i has
been taken into account for further discussion. With receptor
7i, a conspicuous change in color from colorless to yellow was
observed upon the addition of uoride ion. The compound 7i
has also been treated with mixture of anions without (TBAF)
and in the presence of Fꢀ sources. A change in UV spectra
showed the interaction of prob 7i with uoride anion (Fig. S6†).
Upon gradual addition of uoride ion (up to 30 equiv.) a new
absorption band started to appear at 460 nm with a concomitant
decrease in intensity of absorption at 370 nm, as shown in UV-
visible spectra in Fig. 5a. These results indicate the interaction
between receptor and uoride ion which lead to abstraction of
proton from NH group of acridinone scaffold. The changes
induces the ICT transition between nitrogen and carbonyl group
which resulted in new red shi in absorption (lmax 460) and
emission (770 nm) spectra.37 The UV-absorption pattern of
receptor 7l, upon the gradual addition of uoride anion, was
found to be similar to that of 7i (Fig. S3†). Further the absorption
at 460 nm was used to determine binding affinity of receptor and
Fꢀ anion. A Job's plot (Fig. S1†) at total concentration of
receptor-anion (7i and Fꢀ) showed 1 : 1 binding ratio. The
binding constant was calculated using Benesi–Hildebrand
equation38 and was found to be 8.47 ꢂ 102 Mꢀ1 with limit of
detection equal to 5.49 ꢂ 10ꢀ5 M (Fig. S2†). In case of receptor 7l,
the binding constant was found to be 1.14 ꢂ 103 Mꢀ1 and limit
Fig. 4 Fluoride detection by chemosensor 7i (a) without fluoride
anion, (b) naked eye and (c) under UV-light (254 nm); UV-absorption
spectra of 7i and 7l with different anions.
of detection was 9.29 ꢂ 10ꢀ5 M (Fig. S4†). The larger binding
constant value of 4-uoro substituted receptor 7i as compared to
4-chloro 7l may be due to higher electronegativity of uoro group
which enhance the interaction between receptor and anion via
deprotonation of NH group. Moreover, upon diluting the
receptor-uoride ion solution in methanol, absorption intensity
at 360 nm was restored via re-protonation of NH group in the
presence of protic medium (MeOH) (Fig. S1†).
The step-wise addition of uoride ion (up to 10 equiv.) was
also studied using uorescence spectroscopy. In the absence of
any anions, the uorescence spectrum of chemosensor (7i),
upon excitation at 380 nm, showed two emission bands at
450 nm and at 770 nm (Fig. 5b). The emission intensity of band
at 450 nm was found to decrease with increasing concentration
Fig. 3 Different substituted 9-phenyl-acridine-1,8-diones 7a–l.
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protons was observed with increasing addition of uoride ions.
The disappearance of characteristic signal for NH proton as
a result of uoride ion addition, clearly indicates proton
abstraction by uoride ions acting as base. This proton
abstraction by uoride ions seems to be a highly selective
process for uoride ions only (among other anions studied
here). Accordingly this proton abstraction mechanism seems
to be the reason for selective uoride detection by
chemosensor 7i.
Quantum mechanical Density Functional Theory (DFT)
calculations have also been performed to gain further insight
into the structural and spectroscopic changes during complex
formation. As a model, we have optimized the structure of probe
7i and its uoride (7i–Fꢀ) and acetate (7i–OAcꢀ) complexes. We
considered only acetate ion for comparative study with uoride
ion, mainly due to the fact that acetate ion is more basic than all
other anions against which 7i is not responsive. The optimized
geometries are shown in Fig. 7.
The optimized geometries reveal that the N–H bond in 7i has
˚
˚
a bond length of 1.00 A, which is slightly elongated to 1.06 A
upon interaction with acetate ion. The change in N–H bond
distance of the probe on complexation with acetate ions is not
signicant enough to cause corresponding changes in elec-
tronic and spectroscopic properties of the chemosensor (vide
infra). The interaction of uoride ion with N–H proton of the
chemosensor is quite strong. The uoride ion pulls the proton
toward itself and the N–H bond is signicantly elongated to 1.49
˚
˚
A (Fig. 8). The F–H bond length is 1.0 A. The negative charge
generated on the nitrogen in 7i–Fꢀ (as a result of uoride
interaction) is somewhat delocalized on the neighboring alkene
bonds. The delocalization of charge also affects the N–C and
C]C bond lengths. The N–C and C]C bond lengths in 7i–Fꢀ
Fig. 5 (a) Absorption spectra of 7i upon gradual increase of fluoride
addition; (b) fluorescence spectra (excitation at 380 nm) in DMSO as
solvent.
˚
˚
˚
˚
are 1.37 A and 1.43 A compared to 1.40 A and 1.42 A for the
parent compound 7i.
of uoride ions. However, the emission intensity of the band at
770 nm rst increases with the addition of uoride ions from
0.5 to 4.0 equiv., upon further addition of uoride ions, from 6
to 10 equiv., the emission intensity decreases (albeit slightly)
and eventually becomes constant (Fig. 5b).
The strong proton abstraction ability of Fꢀ can be attributed
to the high charge density on uoride ion. The uoride has ꢀ1
charge which is completely localized on it, whereas the negative
charge on acetate ion is more delocalized. The Mulliken charge
analysis reveals that the charge on the oxygen of acetate is
ꢀ0.64, which is considerably smaller than ꢀ1 on uoride. This
difference in charge is most likely to be responsible for
abstraction of proton of acridinedione chemosensor by the
uoride ion.
Binding energies are also calculated in order to rationalize
the stabilities of these complexes. The free energies of interac-
tion of 7i with uoride and acetate ion are ꢀ95.35 and
ꢀ36.50 kcal molꢀ1. The higher interaction energy of 7i with
uoride ion provides the driving force for transfer of proton to
the latter. The interaction energy of uoride ion with 7i is
comparable to a covalent bond (also supported from geometric
analysis) whereas the interaction with acetate ion is in the range
of non-bonding interaction.
In order to further understand the nature and mechanism of
highly selective interaction between the chemosensor 7i and
uoride ions, 1H NMR titrations were performed and spectra
were recorded before and aer adding uoride ions in different
concentrations (1, 2, and 5 equiv.) (Fig. 6). The detailed 1H-NMR
spectrum of 7i (along with structural assignment of peaks) is
given in the experimental section. Fig. 5 shows zoomed-in area
1
of interest (3–10 ppm) in the H-NMR spectrum of 7i. Prior to
1
addition of any uoride ions, the H NMR spectrum for 7i, in
the area selected, shows a sharp singlet for –CH proton at
4.78 ppm, aromatic protons (z6.7–7.2 ppm) are also visible in
this region, the NH proton appears as a singlet at 9.28 ppm
(Fig. 6a). The most noticeable change aer addition of just 1
equiv. of uoride ions, is a drastic decrease in the signal for NH
proton (Fig. 6b); the signal for NH proton completely disappears
aer addition of 2 equiv. of uoride ions (Fig. 6c). Similar
observations were made aer addition of 5 equiv. of uoride
ions. The signal for CH proton at 4.78 ppm remains unaltered. A
minute (insignicant) up-eld chemical shi for aromatic
Finally, the UV-vis spectra are calculated for 7i–Fꢀ and 7i–
OAcꢀ complexes, and compared to the UV-vis spectrum of probe
7i. All complexes show several weak transitions in visible and
near infra-red region but their oscillator strengths are less than
0.05, therefore, these transitions are believed not to play any
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Fig. 6 Study of anion (Fꢀ) addition to probe 7i via 1H NMR spectra; (a) without Fꢀ anion and (b) 1 equiv. (c) 2 equiv. (d) 5 equiv. of Fꢀsource (TBAF)
in DMSO-d6 as solvent.
Fig. 7 Optimized geometries of 7i and its complexes with acetate and fluoride ion, optimized at B3LYP/6-31G(d,p).
signicant role in the observable spectrum. The lmax of 7i is strong absorption band in this region at higher equivalents of
calculated at 322 nm with an oscillator strength of 0.2. Another Fꢀ suggests complexes with more than one uoride per phenyl
peak is present at 326 nm but the oscillator strengths is rela- dihydropyridine unit. Addition of acetate ion to 7i, on the other
tively low (0.0695). These peaks are red shied to 333 and hand, leads to transitions with very low oscillator strength. The
349 nm, respectively for 7i–Fꢀ. The red shiing of the lmax is theoretical ndings are also consistent with the experimental
consistent with the experimental observation where addition of observation where addition of acetate ion leads to quenching of
uoride ion leads to red shi with tail extending to 450 nm UV-vis absorption. Our theoretical and experimental results
(compare Fig. 5a with Fig. 8). The experimental UV-vis spectrum corroborate with each other and provide conclusive evidence
shows relatively strong peak in the region of 400–500 nm upon that the interaction of uoride ion with 7i is different than that
adding 2–10 equivalent of uoride ions. The appearance of for other anions.
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such as basic potassium permanganate or vanillin were also
used. Infrared (IR) spectra were recorded on Bruker Vector-22
spectrometer. The 1H NMR spectra were recorded using
Bruker spectrometers at 300 MHz, 400 MHz, 500 MHz, and 600
MHz, while 13C NMR spectra were recorded at 75 MHz, 100
MHz, 125 MHz, 150 MHz in the appropriate deuterated solvent.
The chemical shis were recorded on the d-scale (ppm) using
1
residual solvents as an internal standard (DMSO; H 2.50, 13C
1
39.43 and CHCl3; H 7.26, 13C 77.16). Coupling constants were
calculated in Hertz (Hz) and multiplicities were labelled s
(singlet), d (doublet), t (triplet), q (quartet), quint (quintet) and
the prexes br (broad) or app (apparent) were used. Mass
spectra (EI+ and FAB) were recorded on Finnigan MAT-321A,
Germany. Melting points of solids were determined using
a Stuart™ melting point SMP3 apparatus.
Fig. 8 Overlay UV-vis absorption spectrum of 7i and fluoride complex
7i–Fꢀ, calculated at TD-B3LYP/6-31G(d,p).
5. Computational methodology
3. Conclusion
All calculations were performed with Gaussian 09 suit of
programs.39 Geometries of phenyl dihydropyridine 7i and its
complexes with uoride and acetate ions are optimized without
any symmetry constraints at B3LYP method of density func-
tional theory at 6-31G(d,p) basis set.40 The B3LYP method
consists of three parameter hybrid functional of Becke41 in
conjunction with the correlation function of Lee et al.42 The
B3LYP method provides a nice balance between cost and
accuracy, and it is known to perform reasonably well for the
prediction of geometries of a number of synthetic,43–46 natural
products47–50 and conjugated systems.51,52 The optimized struc-
tures are conrmed as true minima through frequency calcu-
lations. Absence of any imaginary frequencies conrmed as true
minima. The interaction energies of dihydropyridine with
uoride and acetate ions are calculated by the following equa-
tion Eint ¼ Ecomplex ꢀ (Edhp + Eanion).
In conclusion, a series of acridinediones (7a–l) has been
synthesized using new morpholinium-based ionic uoride
liquids under solvent-free conditions. The acridinediones 7i
and 7l were explored as chemosensors for detection of different
anions such as Fꢀ, OAcꢀ, Brꢀ, Iꢀ, HSO4ꢀ, ClO3ꢀ, ClO4ꢀ, CNꢀ,
and SCNꢀ. A conspicuous change in color from colorless to
yellow, upon addition of uoride ions to acridindione shows
selectivity towards uoride ion detection. This was further
investigated and conrmed via detailed UV-visible, uorescence
and 1H-NMR spectroscopic techniques. The ICT mechanism
responsible for these observed changes was found to be uoride
ion mediated abstraction of NH proton of dihydropyridine part
of acridinedione. Further insight was gained via computational
studies using DFT (B3LYP/6-31G(d,p)), whereupon comparison
of acridinedione interaction with uoride and acetate ion
explained why (and how) it is selective for uoride ion. Our
results provide a strong basis for further modulation and
exploration of acridinediones as non-invasive chemosensors for
uoride ion detection in a variety of sample types (possibly)
including biological samples as well.
Where Ecomplex is the energy of complex formed between
acridinedione and anion whereas Edhp and Eanion are the ener-
gies of isolated acridinedione and anion, respectively. The re-
ported energies of interaction are based on Gibbs free energies.
The spectroscopic properties are calculated in DMSO
solvent. The solvent effect is introduced through IEFPCM
approach, as implemented in Gaussian 09. Time dependent
DFT calculations are performed to calculate the excited state
properties (UV-vis spectra) of these complexes. TD-B3LYP/6-
31G(d,p) method is employed for calculation of UV-vis
spectra. A total of 20 states are calculated with 50:50 single-
4. Material and methods
N-Methyl morphiline ($98.0% (GC)) and N-ethyl morpholine
($97.0% (GC)), n-pentyl bromide, n-heptyl bromide, 5,5-
dimethyl-1,3-cyclohexanedione (95%), substituted benzoni-
triles, trimethylsilyl azide, and silver uoride ($99%) were
purchased from Sigma Aldrich and used directly for carrying
our reaction unless otherwise stated. Toluene (analytical grade),
methanol and distill or Milli-Q water were used as solvents.
Thin layered chromatography was carried out with silica gel 60
t:triplet states. H NMR of the optimized geometries is calcu-
1
lated at B3LYP/6-311+G(2d,p) through GIAO formalism. The 1H
NMR values reported in this study are with reference to TMS.
6. General synthetic procedure for
aluminium-backed plates 0.063–0.200 mm. Analytical grade morpholinium-based ionic liquids
solvents such as ethyl acetate (EtOAc), diethyl ether, hexane and
methanol etc. were used. Round bottomed asks (5, 10, 25, 50,
(MoFs) (3–6)
100, 250 mL) and screw capped micro reaction vessels (3–5 mL) An oven dried round bottom ask was charged with N-alkyl (Me/
were used. For TLC spots visualization, in UV lamp a radiation Et) morpholine (1 g, 10 mmol, 1 equiv.) and toluene (5 mL).
of 254 nm was used. In addition, different staining mixtures, Subsequently, corresponding alkyl (C5, C7) bromide (1.5 equiv.)
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was added to the solution and heated the resulting mixture at 1.58 (2H, m, CH2), 1.35–1.26 (8H, m, (CH2)4), 1.18 (3H, t, J ¼
reux (115–120 ꢁC). The progress of reaction was monitored by 7.2 Hz, CH2–CH3), 0.88 (3H, t, J ¼ 7.2 Hz, CH3); 19F NMR (400
TLC analysis until the complete consumption of starting MHz, DMSO) ꢀ126.9. MS-EI m/z (%), 214.1 (M+ ꢀ Fꢀ, 100).
material. The reaction mixture was cooled to room temperature
and solvent was decanted off. Further, some more cooled
toluene was added, shaken well and removed to get a thick ionic
liquid which was used without purication in the next counter
anion exchange step. The crude mixture of corresponding ionic
7. General procedure for
acridinedione synthesis
In an oven dried ask commercially available dimedone
liquids was dissolved in water (5 mL) and added to the aqueous
(280 mg, 2 mmol), ammonium acetate (77.08 mg, 1 mmol),
solution of AgF (5 mL, 1 equiv.). Subsequently, the precipitates
synthetic morpholinium-IL 3 (191 mg, 1 mmol) were added to
corresponding benzaldehyde derivatives (1 mmol). The reaction
mixture was heated under 125-135 ꢁC until the complete
of silver bromide were removed and water was evaporated via
freeze drying. The residue dissolved in chloroform, ltered and
evaporated by using rotary evaporator. The obtained material
disappearance of starting material monitored by thin layer
was occasionally washed with cooled toluene to get the nal
chromatography (TLC) using ethyl acetate and n-hexane as
desired product. The nal ionic morpholinium-based ionic
a solvent system at different ratio. The reaction mixture was
cooled to room temperature and resultant pure compound was
precipitated by washing crude reaction mixture in ethyl acetate
1
liquids 3–6 were characterized with H, 13C-NMR, IR spectros-
copy and mass spectrometry.
(2 ꢂ 20 mL). While some compounds need column chroma-
6.1. 4-Methyl-4-pentylmorpholin-4-ium uoride (3)
tography for their purication direct aer crude mixture. The
Light brown liquids, (1.70 g, 89%), IR (nmax, cmꢀ1): (solution,
resultant dihydropyridines (7a–7l) were yellow to off-white
solids in different yields (48–78%).
CHCl3) 3405, 2955, 2870, 1630, 1472, 1160. 1H NMR (400 MHz,
DMSO): dH 3.90 (4H, app brs, CH2–O–CH2), 3.45–3.39 (6H, m,
7.1. 9-(40-Methylphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7a)
CH2–N–CH2 & N–CH2), 3.12 (3H, s, N–CH3), 1.71–1.63 (2H, m,
CH2), 1.36–1.23 (4H, m, CH2–CH2), 0.88 (3H, t, J ¼ 7.2 Hz, CH3);
19F NMR (400 MHz, DMSO) ꢀ126.4; 13C NMR (75 MHz, DMSO):
dC 63.8 (CH2), 59.8 (2CH2), 58.9 (2CH2), 46.07 (CH3), 27.9 (CH2),
133 mg (73%); IR (nmax, cmꢀ1): (solid, KBr) 3280, 3065, 2954,
1
2925, 1651, 1607, 1493, 1365, 1220, 1146. H NMR (400 MHz,
1
21.6 (CH2), 20.5 (CH2), 13.8 (CH3). H NMR (400 MHz, DMSO):
DMSO): dH 9.22 (1H, brs, NH), 7.01 (2H, d, J ¼ 8 Hz, ArH), 6.93
(2H, d, J ¼ 8 Hz, ArH), 4.74 (1H, brs, CH-9), 2.42 (2H, d, J ¼
16.8 Hz, CH-4a/5a), 2.29 (2H, d, J ¼ 16.8 Hz, CH-4b/5b), 2.17
(3H, s, ArCH3), 2.14 (2H, d, J ¼ 15.2, CH-2a/7a), 1.95 (2H, d, J ¼
MS-MALDI m/z (%), 172.2 (M+ ꢀ Fꢀ, 100).
6.2. 4-Methyl-4-heptylmorpholin-4-ium uoride (4)
16.4 Hz, CH-2b,7b), 0.99 (6H, s, (CH3)2) 0.84 (6H, s, (CH3)2); 13
C
Brown liquids, (1.90 g, 88%), IR (nmax, cmꢀ1): (solution, CHCl3)
3416, 2928, 2863, 1632, 1471, 1119. 1H NMR (400 MHz, DMSO):
dH 3.90 (4H, app brs, CH2–O–CH2), 3.45–3.39 (6H, m, CH2–N–
CH2 & N–CH2), 3.12 (3H, s, N–CH3), 1.68–1.64 (2H, m, CH2), 1.26
(8H, m, (CH2)4), 0.88 (3H, t, J ¼ 7.2 Hz, CH3); 13C NMR (100
MHz, DMSO): dC 63.8 (CH2), 59.8 (2CH2), 58.9 (2CH2), 46.03
(CH3), 31 (CH2), 28.2 (CH2), 25.7 (CH2), 21.9 (CH2), 20.7 (CH2),
13.9 (CH3). MS-MALDI m/z (%), 199.5 (M+ ꢀ Fꢀ, 100).
NMR (125 MHz, DMSO): dC 194.3 (2CO), 149.1 (2C), 144.3 (C),
134.2 (C), 128.1 (2CH), 127.5 (2CH), 111.6 (2C), 50.2 (2CH2), 39.6
(2CH2), 32.4 (CH), 32.1 (2C), 29.1 (2CH3), 26.4 (2CH3), 20.5
(ArCH3). MS-EI m/z 363.3 (M+). The data is identical to those
previously reported.53
7.2. 9-(40-Hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7b)53
132 mg, (82%); IR (nmax, cmꢀ1): (solid, KBr) 3276, 3198, 2956,
1613, 1471, 1372, 1223, 1141. 1H NMR (300 MHz, DMSO): dH 9.17
(1H, brs, NH), 8.96 (1H, brs, ArOH), 7.01 (2H, d, J ¼ 8.4 Hz, ArH),
6.93 (2H, d, J ¼ 8.4 Hz, ArH), 4.69 (1H, brs, CH-9), 2.42 (2H, d, J ¼
16.8 Hz, CH-4a/5a), 2.28 (2H, d, J ¼ 16.8 Hz, CH-4b/5b), 2.14 (2H,
d, J ¼ 16.2 Hz, CH-2a/7a), 1.95 (2H, d, J ¼ 16.2 Hz, CH-2b,7b),
0.99 (6H, s, (CH3)2) 0.86 (6H, s, (CH3)2); 13C NMR (125 MHz,
DMSO): dC 194.3 (2CO), 154.2 (C), 148.87 (2C), 137.9 (C), 128.4
(2CH), 114.2 (2CH), 111.8 (2C), 50.1 (2CH2), 39.5 (2CH2), 32.1
(2C), 31.6 (CH), 29.1 (2CH3), 26.4 (2CH3). MS-EI m/z 365.2 (M+);
EI-HRMS (M+) C23H27O3N found 365.2001, calculated 365.1985.
6.3. 4-Ethyl-4-pentylmorpholin-4-ium uoride (5)
Light brown liquids, (1.30 g, 73%), IR (nmax, cmꢀ1): (solution,
CHCl3) 3451, 2957, 2872, 1635, 1473, 1123. 1H NMR (400 MHz,
DMSO): dH 3.90 (4H, app d, J ¼ 2.4 Hz CH2–O–CH2), 3.48 (2H, q,
J ¼ 7.2 Hz, CH2–CH3), 3.43–3.35 (6H, m, CH2–N–CH2 & N–CH2),
1.61–1.57 (2H, m, CH2), 1.35–1.26 (8H, m, (CH2)2), 1.18 (3H, t, J
¼ 7.2 Hz, CH2–CH3), 0.88 (3H, t, J ¼ 7.2 Hz, CH3); 13C NMR (100
MHz, DMSO): dC 61.4 (2CH2), 58.9 (2CH2 & CH2), 54.9 (CH2),
29.7 (CH2), 23.5 (CH2), 22.1 (CH2), 15.7 (CH3), 8.64 (CH3). MS-
MALDI m/z (%), 186.2 (M+ ꢀ Fꢀ, 100).
6.4. 4-Ethyl-4-heptylmorpholin-4-ium uoride (6)
7.3. 9-(30-Hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7c)
Light brown liquids, (1.43 g, 71%), IR (nmax, cmꢀ1): (solution,
CHCl3) 3403, 2929, 2864, 1666, 1595, 1454. 1H NMR (300 MHz,
DMSO): dH 3.88 (4H, app brs, CH2–O–CH2), 3.48 (2H, q, J ¼ 139 mg, (86%); IR (nmax, cmꢀ1): (solid, KBr) 3283, 3207, 3072,
1
7.2 Hz, CH2–CH3), 3.43–3.35 (6H, m, CH2–N–CH2 & N–CH2), 2960, 2929, 1620, 1482, 1365, 1223, 1143. H NMR (400 MHz,
2000 | RSC Adv., 2018, 8, 1993–2003
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7.7. 9-(20-Methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7g)
DMSO): dH 9.23 (1H, brs, NH), 9.02 (1H, brs, ArOH), 6.90 (1H, t,
J ¼ 7.6 Hz, ArH), 6.61 (1H, brs, ArH), 6.55 (1H, d, J ¼ 7.6 Hz,
ArH), 6.40 (1H, d, J ¼ 8 Hz, ArH), 4.70 (1H, brs, CH-9), 2.42 (2H,
d, J ¼ 17.2 Hz, CH-4a/5a), 2.28 (2H, d, J ¼ 17.2 Hz, CH-4b/5b),
2.14 (2H, d, J ¼ 16 Hz, CH-2a/7a), 1.95 (2H, d, J ¼ 16.4 Hz, CH-
2b/7b), 0.99 (6H, s, (CH3)2) 0.87 (6H, s, (CH3)2); MS-EI m/z 365.2
(M+); EI-HRMS (M+) C23H27O3N found 365.1962, calculated
365.1985.
128 mg, (67%); IR (nmax, cmꢀ1): (solid, KBr) 3271, 3174, 3058,
2952, 1643, 1601, 1365, 1218, 1142. 1H NMR (400 MHz, DMSO):
dH 9.16 (1H, brs, NH), 7.15 (1H, d, J ¼ 6.4 Hz, ArH), 6.99 (1H, t, J
¼ 7.2 Hz, ArH), 6.78 (1H, d, J ¼ 8.4 Hz, ArH), 6.71 (1H, t, J ¼
7.2 Hz, ArH), 4.90 (1H, brs, CH-9), 3.65 (3H, s, OCH3), 2.40 (2H,
d, J ¼ 16.8 Hz, CH-4a/5a), 2.21 (2H, d, J ¼ 16.8 Hz, CH-4b/5b),
2.09 (2H, d, J ¼ 16.4 Hz, CH-2a/7a), 1.87 (2H, d, J ¼ 16 Hz,
CH-2b/7b), 0.99 (6H, s, (CH3)2) 0.87 (6H, s, (CH3)2); 13C NMR
(125 MHz, DMSO): dC 194 (2CO), 157.6 (C), 149.6 (2C), 133.8 (C),
131.4 (CH), 126.6 (CH), 119.1 (CH), 110.8 (CH), 110.1 (2C), 55
(OCH3), 50.4 (2CH2), 39.5 (2CH2), 31.9 (2C), 31.4 (CH), 29.2
(2CH3), 25.9 (2CH3). MS-EI m/z 379.3 (M+); EI-HRMS (M+)
7.4. 9-(30-Ethoxy-40-hydroxyphenyl)-3,3,6,6-tetramethyl-
3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (7d)
146 mg, (71%); IR (nmax, cmꢀ1): (solid, KBr) 3273, 3202, 3071,
2961, 1617, 1481, 1366, 1223, 1149. 1H NMR (400 MHz, DMSO):
dH 9.19 (1H, brs, NH), 8.47 (1H, brs, ArOH), 6.68 (1H, s, ArH),
6.53 (1H, d, J ¼ 8.4 Hz, ArH), 6.49 (1H, d, J ¼ 8.4 Hz, ArH), 4.69
(1H, brs, CH-9), 3.87 (2H, q, J ¼ 7.2 Hz, CH2–CH3), 2.42 (2H, d, J
¼ 17.2 Hz, CH-4a/5a), 2.28 (2H, d, J ¼ 16.8 Hz, CH-4b/5b), 2.14
(2H, d, J ¼ 16 Hz, CH-2a/7a), 1.95 (2H, d, J ¼ 16 Hz, CH-2b/7b),
1.27 (3H, t, J ¼ 7.2 Hz, CH2–CH3), 0.99 (6H, s, (CH3)2) 0.87 (6H, s,
(CH3)2); 13C NMR (100 MHz, DMSO): dC 194.4 (2CO), 148.9 (2C),
145.6 (C0), 144.7 (C), 138.4 (C), 119.8 (CH), 114.8 (CH), 113.8
(CH), 111.7 (2C), 63.8 (CH2), 50.3 (2CH2), 39.5 (2CH2), 32.1 (2C),
31.8 (CH), 29.1 (2CH3), 26.3 (2CH3), 14.7 (CH3). MS-EI m/z 409.3
(M+); EI-HRMS (M+) C25H32O4N found 409.2258, calculated
409.2248.
C
24H29O3N found 379.2162, calculated 379.2142.
7.8. 9-(20,30,40-Trimethoxyphenyl)-3,3,6,6-tetramethyl-
3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (7h)
172 mg, (78%); Mp 246–250 ꢁC, IR (nmax, cmꢀ1): (solid, KBr) 3306,
1
3190, 3069, 2954, 1640, 1609, 1224, 1097. H NMR (400 MHz,
DMSO): dH 9.14 (1H, brs, NH), 6.79 (1H, d, J ¼ 8.8 Hz, ArH), 6.54
(1H, t, J ¼ 8.8 Hz, ArH), 4.88 (1H, brs, CH-9), 3.80 (3H, s, OCH3),
3.68 (3H, s, OCH3), 3.63 (3H, s, OCH3), 2.38 (2H, d, J ¼ 17.2 Hz,
CH-4a/5a), 2.24 (2H, d, J ¼ 17.2 Hz, CH-4b/5b), 2.09 (2H, d, J ¼
16 Hz, CH-2a/7a), 1.87 (2H, d, J ¼ 16 Hz, CH-2b/7b), 0.98 (6H, s,
(CH3)2) 0.88 (6H, s, (CH3)2); 13C NMR (75 MHz, DMSO): dC 194.1
(2CO), 151.5 (C), 151.3 (C), 149.2 (2C), 133.8 (C), 132.5 (C), 124.8
(CH), 110.1 (2C), 106.4 (CH), 60.3 (OCH3), 59.8 (OCH3), 55.6
(OCH3), 50.4 (2CH2), 39.5 (2CH2), 32 (2C), 29.6 (CH-9), 29.2
(2CH3), 25.9 (2CH3). MS-EI m/z 439.3 (M+); EI-HRMS (M+)
C26H33O5N found 439.2333, calculated 439.2353.
7.5. 9-(40-Methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7e)53
140 mg, (73%); IR (nmax, cmꢀ1): (solid, KBr) 3277, 3207, 2956,
1
2930, 1644, 1607, 1481, 1366, 1224, 1141. H NMR (400 MHz,
DMSO): dH 9.22 (1H, brs, NH), 7.03 (2H, d, J ¼ 8.8 Hz, ArH), 6.69
(2H, d, J ¼ 8.4 Hz, ArH), 4.73 (1H, brs, CH-9), 3.64 (3H, s, OCH3),
2.42 (2H, d, J ¼ 17.2 Hz, CH-4a/5a), 2.28 (2H, d, J ¼ 17.2 Hz, CH-
4b/5b), 2.14 (2H, d, J ¼ 16 Hz, CH-2a/7a), 1.95 (2H, d, J ¼ 16 Hz,
CH-2b/7b), 0.99 (6H, s, (CH3)2) 0.86 (6H, s, (CH3)2); 13C NMR
(125 MHz, DMSO): dC 194.3 (2CO), 157.1 (C), 148.9 (2C), 139.5
(C), 128.5 (2CH), 112.9 (2CH), 111.7 (2C), 54.8 (OCH3), 50.2
(2CH2), 39.5 (2CH2), 32.1 (2C), 31.9 (CH), 29.1 (2CH3), 26.4
(2CH3). MS-EI m/z 379.1 (M+); EI-HRMS (M+) C24H29O3N found
379.2155, calculated 379.2142.
7.9. 9-(40-Fluorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7i)
137 mg, (75%); IR (nmax, cmꢀ1): (solid, KBr) 3528, 3346, 3275,
1
3164, 3045, 2956, 1613, 1486, 1366, 1221, 1146. H NMR (400
MHz, DMSO): dH 9.29 (1H, brs, NH), 7.14 (2H, dd, J ¼ 8, 6 Hz,
ArH), 6.96 (2H, t, J ¼ 8.8 Hz, ArH), 4.78 (1H, brs, CH-9), 2.42 (2H,
d, J ¼ 17.2 Hz, CH-4a/5a), 2.31 (2H, d, J ¼ 17.2 Hz, CH-4b/5b),
2.18 (2H, d, J ¼ 16 Hz, CH-2a/7a), 1.87 (2H, d, J ¼ 16 Hz, CH-
2b/7b), 0.99 (6H, s, (CH3)2) 0.88 (6H, s, (CH3)2); 13C NMR (75
MHz, DMSO): dC 194.2 (2CO), 161.8/158.6 (C), 149.3 (2C), 143.3
(C), 129.2/129.1 (2CH), 114.3/114.9 (2CH), 111.3 (2C), 50.2
(2CH2), 39.5 (2CH2), 32.2 (CH-9), 32.1 (2C), 29.2 (2CH3), 25.9
(2CH3). MS-EI m/z 367.3 (M+); EI-HRMS (M+) C23H26O2NF found
367.1921, calculated 367.1942.
7.6. 9-(30-Bromo-40-methoxyphenyl)-3,3,6,6-tetramethyl-
3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (7f)
170 mg, (74%); IR (nmax, cmꢀ1): (solid, KBr) 3282, 3213, 2962, 2925,
1650, 1610, 1486, 1363, 1218, 1136. 1H NMR (300 MHz, DMSO): dH
9.29 (1H, brs, NH), 7.26 (1H, d, J ¼ 2.1 Hz, ArH), 7.06 (1H, dd, J ¼
8.4, 2.1 Hz, ArH), 6.90 (1H, d, J ¼ 8.4 Hz, ArH), 4.71 (1H, brs, CH-
9), 3.64 (3H, s, OCH3), 2.42 (2H, d, J ¼ 17.1 Hz, CH-4a/5a), 2.30
(2H, d, J ¼ 17.1 Hz, CH-4b/5b), 2.16 (2H, d, J ¼ 16.2 Hz, CH-2a/7a),
7.10. 9-(30-Nitrophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7j)53
1.95 (2H, d, J ¼ 16 Hz, CH-2b/7b), 0.99 (6H, s, (CH3)2) 0.87 (6H, s, 124 mg, (63%); IR (nmax, cmꢀ1): (solid, KBr) 3176, 2926, 2857,
(CH3)2); 13C NMR (125 MHz, DMSO): dC 194.3 (2CO), 153.2 (C), 1647, 1607, 1532, 1399, 1222, 1145. 1H NMR (400 MHz, DMSO):
149.3 (2C), 141 (C), 131.9 (CH), 127.8 (CH), 111.9 (CH), 111.1 (2C), dH 9.45 (1H, brs, NH), 7.95 (1H, s, ArH), 7.93 (1H, d, J ¼ 12.4 Hz,
109.6 (C), 55.9 (OCH3), 50.2 (2CH2), 39.5 (2CH2), 32.1 (2C), 31.9 ArH), 7.60 (1H, d, J ¼ 7.6 Hz, ArH), 7.49 (1H, t, J ¼ 8 Hz, ArH),
(CH), 29.1 (2CH3), 26.4 (2CH3). MS-EI m/z 458.1 (M+); EI-HRMS 4.91 (1H, brs, CH-9), 2.46 (2H, d, obscured by DMSO signal),
(M+) C24H28O3NBr found 457.1240, calculated 457.1247.
2.35 (2H, d, J ¼ 17.2 Hz, CH-4b/5b), 2.18 (2H, d, J ¼ 16 Hz, CH-
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2a/7a), 1.87 (2H, d, J ¼ 16 Hz, CH-2b/7b), 1.01 (6H, s, (CH3)2)
0.85 (6H, s, (CH3)2); MS-EI m/z 394.2 (M+); EI-HRMS (M+)
6 U. N. Yadav, P. Pant, D. Sharma, S. K. Sahoo and
G. S. Shankarling, Sens. Actuators, B, 2014, 197, 73–80.
7 X. Shang, Z. Yang, J. Fu, P. Zhao and X. Xu, Sensors, 2015, 15,
28166–28176.
C
23H26O2N2 found 394.1891, calculated 394.1887.
8 A. Wiegand and T. Attin, Oral Health Prev. Dent., 2003, 1, 245–
253.
9 S. Peckham and N. Awofeso, Sci. World J., 2014, 2014, 1–10.
10 G. Sivaraman and D. Chellappa, J. Mater. Chem. B, 2013, 1,
5768–5772.
7.11. 9-(30-Cyanophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7k)
127 mg, (67%); IR (nmax, cmꢀ1): (solid, KBr) 3300, 3232, 3088,
1
2956, 2892, 2233, 1644, 1486, 1365, 1221, 1141. H NMR (400
MHz, DMSO): dH 9.39 (1H, brs, NH), 7.52–7.46 (3H, m, ArH),
7.39 (1H, app t, J ¼ 8.4 Hz, ArH), 4.82 (1H, brs, CH-9), 2.46 (2H,
d, obscured by DMSO signal), 2.36 (2H, d, J ¼ 17.2 Hz, CH-4b/
5b), 2.18 (2H, d, J ¼ 16.4 Hz, CH-2a/7a), 1.87 (2H, d, J ¼
´
´
11 M. M. M. Raposo, B. Garcıa-Acosta, T. Abalos, P. Calero,
´
´~
R. n. Martınez-Manez, J. V. Ros-Lis and J. Soto, J. Org.
Chem., 2010, 75, 2922–2933.
12 L. E. Santos-Figueroa, M. E. Moragues, M. M. M. Raposo,
16.4 Hz, CH-2b/7b), 1.00 (6H, s, (CH3)2) 0.85 (6H, s, (CH3)2); 13
C
´
R. M. Batista, S. P. Costa, R. C. M. Ferreira, F. Sancenon,
NMR (75 MHz, DMSO): dC 194.3 (2CO), 149.9 (2C), 148.4 (C),
132.5 (2CH), 131 (2CH), 129.4 (CH), 128.9 (CH), 118.9 (C), 110.5
(2C), 110.4 (C), 50 (2CH2), 39.5 (2CH2), 33.7 (CH), 33.3 (2C), 29.2
(2CH3), 25.9 (2CH3). MS-EI m/z 375.3 (M+); EI-HRMS (M+)
´
´˜
R. Martınez-Manez, J. V. Ros-Lis and J. Soto, Org. Biomol.
Chem., 2012, 10, 7418–7428.
13 W. Radchatawedchakoon, W. Sangsuwan, S. Kruanetr and
U. Sakee, Spectrochim. Acta, Part A, 2014, 121, 306–312.
14 C. Yang, M. Zheng, Y. Li, B. Zhang, J. Li, L. Bu, W. Liu,
M. Sun, H. Zhang and Y. Tao, J. Mater. Chem. A, 2013, 1,
5172–5178.
15 Q. K. Sun, M. S. Chen, Z. W. Liu, H. C. Zhang and W. J. Yang,
Tetrahedron Lett., 2017, 58, 2711–2714.
16 V. Karunakaran, P. Ramamurthy, T. Josephrajan and
V. Ramakrishnan, Spectrochim. Acta, Part A, 2002, 58, 1443–
1451.
C
24H26O2N2 found 374.1978, calculated 374.1989.
7.12. 9-(40-Chlorophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (7l)53
150 mg, (78%); IR (nmax, cmꢀ1): (solid, KBr) 3276, 3177, 3059,
1
2875, 1647, 1609, 1491, 1365, 1221, 1145. H NMR (500 MHz,
DMSO): dH 9.34 (1H, brs, NH), 7.20 (2H, d, J ¼ 8.5 Hz, ArH), 7.13
(2H, d, J ¼ 8.5 Hz, ArH), 4.77 (1H, brs, CH-9), 2.42 (2H, d, J ¼
17 Hz, CH-4a/5a), 2.31 (2H, d, J ¼ 17 Hz, CH-4b/5b), 2.18 (2H, d,
J ¼ 16 Hz, CH-2a/7a), 1.87 (2H, d, J ¼ 16 Hz, CH-2b/7b), 0.99
(6H, s, (CH3)2) 0.84 (6H, s, (CH3)2); 13C NMR (125 MHz, DMSO):
dC 194.4 (2CO), 149.5 (2C), 146.1 (C), 129.6 (C), 129.5 (2CH),
127.6 (2CH), 111.1 (2C), 50.2 (2CH2), 39.5 (2CH2), 32.6 (CH), 32.1
(2C), 29.2 (2CH3), 25.9 (2CH3). MS-EI m/z 382.9 (M+); EI-HRMS
(M+) C23H26O2NCl found 383.1629, calculated 383.1647.
17 N. Srividya, P. Ramamurthy and V. Ramakrishnan,
Spectrochim. Acta, Part A, 1998, 54, 245–253.
´
18 J.-P. Fouassier, F. Morlet-Savary, J. Lalevee, X. Allonas and
C. Ley, Materials, 2010, 3, 5130–5142.
19 P. Xiao, F. Dumur, M.-A. Tehfe, B. Graff, D. Gigmes,
´
J. P. Fouassier and J. Lalevee, Polymer, 2013, 54, 3458–3466.
20 B. Venkatachalapathy, P. Ramamurthy and
V. Ramakrishnan, J. Photochem. Photobiol., A, 1997, 111,
163–169.
Conflicts of interest
21 A. Madaan, R. Verma, V. Kumar, A. T. Singh, S. K. Jain and
M. Jaggi, Arch. Pharm., 2015, 348, 837–860.
22 K. Sirisha, G. Achaiah and V. M. Reddy, Arch. Pharm., 2010,
343, 342–352.
The authors have declared no conict of interest.
23 A. R. Trivedi, D. K. Dodiya, B. H. Dholariya, V. B. Kataria,
V. R. Bhuva and V. H. Shah, Bioorg. Med. Chem. Lett., 2011,
21, 5181–5183.
24 H. Haller, Int. J. Clin. Pract., 2008, 62, 781–790.
25 S. Bahekar and D. Shinde, Acta Pharm., 2002, 52, 281–287.
26 R. Velu, N. Won, J. Kwag, S. Jung, J. Hur, S. Kim and N. Park,
New J. Chem., 2012, 36, 1725–1728.
27 M. Zheng, M. Sun, D. Zhang, T. Liu, S. Xue and W. Yang, Dyes
Pigm., 2014, 101, 109–115.
28 P. Ashokkumar, V. Ramakrishnan and P. Ramamurthy, J.
Phys. Chem. B, 2010, 115, 84–92.
Acknowledgements
We are thankful to Higher Education Commission (HEC) with
grant number 20-4732, Pakistan for providing nancial support
for this project.
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