Design, synthesis and photoluminescent studies of new 1,5-benzodiazepines derivatives: Towards new ESIPT compounds

Article abstract of DOI:10.1016/j.tet.2021.132078

A series of novel N₁-triazolo-4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-ones 7a-e and N₅-triazolo-4-(2-acetoxyphenyl)-1,5-benzodiazepin-2-ones 8a-e were designed and synthesized in good yields via a Cu(I) catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC) between the N₁- and N₅-propargyl-1,5-benzodiazepines 2 and 5 respectively and various arylazides 6a-e. Photophysical properties were investigated for all the obtained triazolo-benzodiazepine hybrids by mean of absorption and fluorescence spectral techniques. Thus, a fluorescent emission was detected for the derivatives 7a-e in aggregated state. On another hand, the O-acetylated derivatives 8a-e were found to be not emissive. Finally, we have chosen a model reaction to demonstrate that upon deprotecting the -OAc group in the N₁, N₅-disubstituted benzodiazepine 8d a moderate fluorescence reappeared in the obtained product 9d proving that an ESIPT process can take place as long as the hydroxyl group remains free, allowing the OH/C[dbnd]O proton transfer to occur. A computational study of compounds 7e and 9d in vacuo provide further details and arguments to rationalize the fluorescence of these compounds in aqueous mixtures.

Full text of DOI:10.1016/j.tet.2021.132078

Tetrahedron 86 (2021) 132078
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Design, synthesis and photoluminescent studies of new 1,5-
benzodiazepines derivatives: Towards new ESIPT compounds
a
,
c
b
c
b
Chiraz Ismaila , Hasan Mtiraoui , Jean-Yves Winum , Moncef Msaddek ,
,
*
Rafik Gharbi
a
University of Monastir, Research Unit of Applied Chemistry and Environment/ UR13ES63, Department of Chemistry, Faculty of Sciences of Monastir, 5000,
Monastir, Tunisia
University of Monastir, Laboratory of Heterocyclic Chemistry Natural Products and Reactivity/CHPNR, Department of Chemistry, Faculty of Sciences of
b
Monastir, 5000, Monastir, Tunisia
c
IBMM, Univ Montpellier, CNRS, ENSCM, 34296, Montpellier, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 November 2020
Received in revised form
A series of novel N -triazolo-4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-ones 7a-e and N -triazolo-4-(2-
1
5
acetoxyphenyl)-1,5-benzodiazepin-2-ones 8a-e were designed and synthesized in good yields via a Cu(I)
catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC) between the N - and N -propargyl-1,5-
1
5
3
March 2021
benzodiazepines 2 and 5 respectively and various arylazides 6a-e. Photophysical properties were
investigated for all the obtained triazolo-benzodiazepine hybrids by mean of absorption and fluores-
cence spectral techniques. Thus, a fluorescent emission was detected for the derivatives 7a-e in aggre-
gated state. On another hand, the O-acetylated derivatives 8a-e were found to be not emissive. Finally, we
Accepted 7 March 2021
Available online 11 March 2021
Keywords:
1 5
have chosen a model reaction to demonstrate that upon deprotecting the -OAc group in the N , N -
1,5-benzodiazepin-2-ones
disubstituted benzodiazepine 8d a moderate fluorescence reappeared in the obtained product 9d
proving that an ESIPT process can take place as long as the hydroxyl group remains free, allowing the OH/
C]O proton transfer to occur. A computational study of compounds 7e and 9d in vacuo provide further
details and arguments to rationalize the fluorescence of these compounds in aqueous mixtures.
1
,2,3-triazolo-benzodiazepines
Click-chemistry
Photophysical properties
Fluorescence
Excited-state intramolecular proton transfer
©
2021 Elsevier Ltd. All rights reserved.
(
ESIPT)
2
009 Elsevier Ltd. All rights reserved.
induced electron transfer (PET) [14], intramolecular charge trans-
fer (ICT) [15], twisted intramolecular charge transfer (TICT) [16],
fluorescence resonance energy transfer (FRET) [17], metal-ligand
charge transfer (MLCT) [18], electronic energy transfer (EET) [19],
and excited-state intramolecular proton transfer (ESIPT) [20] have
been given as logical explanations especially when unexpected
luminescent behaviors were detected.
1
. Introduction
Over the past decade, the fluorescence phenomenon has often
been highlighted owing to the fact that a great number of re-
searchers made a more frequent use of such spectroscopic tech-
nologies [1e4]. Indeed, the molecular fluorescence has proven to be
attractive due to its efficiency in various fields of medicinal sciences
research as an important diagnostic versatile tool [5e8]. Recently,
the appearance of useful and well-designed fluorescent probes has
accelerated exhaustively the development of new techniques in life
science technology [9e12]. Among these probes, many privileged
heterocyclic structures were found to exhibit fluorescence and have
been successfully tested for their photoluminescent properties [13].
In this context, different sensing mechanisms such as photo-
As a part of our research program directed on the design and
synthesis of molecular hybrids built around the 1,5-benzodiazepine
(BZD) scaffold [21e24], H. Mtiraoui et al. [25], have recently
explored the photoluminescent properties of some 1,5-
benzodiazepin-2-one analogs finding that the synthesized ana-
logs were emissive in the aggregated and solid state. As depicted
below, an intramolecular OeH/N hydrogen-bonding within the
heterocycle 1 enabled a proton transfer (ESIPT) process and was
given by the authors as the main explanation for the photo-
luminescence occurring (Scheme 1).
Thereby, we have used the already described 4-(2-
hydroxyphenyl)- 1,3-dihydro-1,5-benzodiazepin-2-one 1 [26], as a
*
Corresponding author.
E-mail address: rafikgharbifsm16@gmail.com (R. Gharbi).
https://doi.org/10.1016/j.tet.2021.132078
040-4020/© 2021 Elsevier Ltd. All rights reserved.
0

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
Scheme 1. The ESIPT process for compound 1.
Scheme 2. N-alkylation of benzodiazepine 1.
useful key-intermediate to develop synthetic routes to a series of
- or N -heteroaryl moieties, in particular triazole moieties, linked
N
1
5
to the 1,5-benzodiazepine nucleus with the purpose to further
study their photophysical properties. Indeed, triazole moieties
linked to some derivatives have been well explored and investi-
gated for their optical properties via different sensing mechanisms
[
27,28]. Thus, the particular purpose was to see to what extent, the
structural modifications introduced on the BZD ring and the
changing of the solvent’s nature might affect the ESIPT process
occurrence. The first idea was, then, to confirm what was previously
described by H. Mtiraoui et al. [25], namely the systematic occur-
1
rence of an ESIPT process in the case of N -functionalized BZDs 1
analogs. The second goal was then to further develop the work with
a view to study the fluorescence behaviors of the differently
substituted synthesized BZD derivatives. Especially in the case of
5
the N -functionalized BZD the changes in the fluorescence behav-
iors in relation to the availability (or not) of a free OeH group have
been the subject of interesting studies. We describe herein the
obtained results.
2
. Results and discussions
Starting from the 1,5-benzodiazepine-one 1, we have targeted
novel hybrids linking the triazole moiety at different positions of
the BZD ring. Consequently, since the well-known alkyne/azide
Cu(I) catalyzed 1,3-dipolar cycloaddition reaction seemed then to
be the most appropriate methodology for an easy access to such
scaffolds [22,23], we first planned to perform regiospecific func-
Scheme 3. Synthesis of compound 5.
5
to increase the nucleophilicity of the nitrogen N . Thus, the O-
acetylation was then achieved in the presence of an excess of acetic
anhydride and trimethylamine allowing the reaction mixture to stir
overnight at room temperature. Let’s point out here that based on a
TLC control, we have noticed that the fluorescence effect observed
for compound 3 disappeared in the case of the acetylated analogs 4.
The suppression of the intramolecular OeH/N hydrogen-bond
seems obvious since it suggests the impossibility of the establish-
ment of an ESIPT process. In the next step, the deprotonation of the
tionalizations (propargylation) of the amidic nitrogen (N
1
) or the
iminic one (N ). To the best of our knowledge, the study of the
5
selective propargylation from either of the two nitrogens in BZD 1
has not yet been described.
We have first achieved the N
basic conditions (NaH in THF) [29]. Indeed, the use of such chemical
conditions prevented the non-desired N -alkylation to take place.
Undoubtedly, here the hydroxyl hydrogen is involved in an intra-
molecular hydrogen-bond with the iminic nitrogen N and thereby
1
-propargylation of 1 using mild
5
methylene at C
lowed by a subsequent nucleophilic substitution of the negatively
charged nitrogen N on the propargyl bromide. The crude was
purified on a chromatographic column (cyclohexane/ethyl acetate/
:4) and compound 5 was recovered in good yield as a pure form
3
led to a mesomeric destabilized anionic form fol-
5
dramatically reduces the nucleophilicity of this latter. The reaction,
monitored by TLC, showed the formation of a sole product which
was identified on the basis of its spectral data as the N-prop-2-yn-
yl- 1,5-benzodiazepin-2-one 2 (Scheme 2).
In the second stage of the work we had to develop an adequate
methodology to perform a specific propargylation at the 5-position
of BZD 1. So as described in Scheme 3, a preliminary protective
methylation of the amidic nitrogen was necessary. This reaction led
quantitatively to the nitrogenated diazepine 3. Here, the fact that
we have not detected any trace of the side O-alkylation-product
because of the reluctance of the oxygen atom to react can be
rationalized in terms of the Hard and Soft Acid and Base principle
5
6
(Scheme 3).
Once prepared, both key-intermediates 2 and 5 were reacted
following the CuAAC procedure [22,23] (Scheme 4) with a series of
arylazides 6(aee) (1,3-dipoles) prepared according to the proced-
ure described by Kamalraj et al. [30]. (Table 1). The % yield of each
triazole product in Scheme 4 is depicted in Table 2.
At this stage of the work we were prompted to record the ab-
sorption and emission spectra for all prepared cycloadducts 7 and
8
. Our study was then firstly focused on the emission behavior of
the N -triazolo-1,5-benzodiazepin-2-ones 7 in the aggregated
[
29].
The next step was then to deactivate the hydroxyl group in order
1
2

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
Scheme 4. Synthesis of compounds 7a-e and 8a-e.
Table 1
Table 3
One-pot synthesis of azides 6a and 6(bee).
2
Photophysical data for compounds 7(aee) and 8(aee) in THF/H O mixture.
Entry
n
R
1
R
2
Entry
labs (nm)
lem (nm)
Stokes Shift (nm)
F
F
6
6
6
6
6
a
b
c
d
e
1
0
0
0
0
H
H
CH
H
H
H
CH
CH
OCH
Cl
7a
7b
7c
7d
7e
262
261
260
238
236
229
236
249
238
243
381
380
381
381
380
a
a
a
a
a
119
119
121
143
144
b
b
b
b
b
0,14d
0,16d
0,14d
3
3
3
d
3
0,21
0,43d
8
8
8
8
8
a
b
c
d
e
c
c
c
c
c
Table 2
One-pot synthesis of 1,4-disubstituted 1,2,3-triazole 7e8.
a
b
c
Entry
n
R
1
R
2
Yield (%)
not applicable.
not determined.
not fluorescent.
7
7
7
7
7
8
8
8
8
8
a
b
c
d
e
a
b
c
1
0
0
0
0
1
0
0
0
0
H
H
CH
H
H
H
H
CH
H
H
H
CH
CH
OCH
Cl
H
CH
CH
OCH
Cl
69
71
82
65
83
73
70
64
85
78
3
3
d
ꢀ
Measurement determined at 25 C by a relative method using quinine sulfate as
3
3
standard (
F
F
¼ 0.52 in 0.05 M H
2 4
SO ) [31].
3
3
them more emissive. Consequently, the luminescence here would
therefore be related to an ESIPT mechanism initiated a strong in-
ternal hydrogen bond interaction N—HO in the aggregated state as
driving force. Moreover, the rigidity of the conformations adopted
by structures 7 presumably favored the formation of a radiative 6-
membered ring H-bonding system responsible for the ESIPT effect.
3
3
d
e
state. It then turned out that all the derivatives are emissive and
tend to exhibit an encouraging quantum yield ranging from 0.14 to
.43 with a large stokes shift around 140 nm registered in water
As summarized in Table 2, in a THF/H
a-e were all emissive however displaying different bands’ in-
tensities that appear approximatively at the same em (Fig. 1). Thus,
2
O mixture, compounds
7
0
l
with 1% (v/v) of tetrahydrofuran (Table 3). Let us notice that under
such conditions we have reach the highest intensity for the fluo-
rescence emission. Indeed, H. Mtiraoui et al., have reported the
fluorescence absorption and emission data for compound 1,
recorded in the solid state (quantum yield ¼ 0.26 and stokes shift
around 175 nm) and in different THF-water solution percentages. It
has been determined that when using high water percentages, the
emission of compound 1 would increase [25]. Same process for
compounds 7(aee), in an aqueous medium containing 1% (v/v) of
THF, we have obtained the highest emission intensities. This is
undoubtedly due to the formation of insoluble aggregates making
while derivatives 7e and 7d were found to have the highest
quantum yields: 0.43 and 0.21 respectively, compounds 7a, 7b and
7c were less emissive exhibiting nearly the same quantum yields
values. It is then thinkable that these yields variation are closely
related to the electro-donating or electro-attracting nature effects
of the R
Contrary to the above described results, no fluorescence phe-
nomena were detected for the N -triazolo-1,5-benzodiazepin-2-
1 2
and R alkyl groups.
5
ones series 8a-e neither in the aggregated state nor in solution.
As anticipated above, the O-protective acetylation prevented here
the establishment of hydrogen bonding to occur and consequently
3

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
Scheme 6. The ESIPT mechanism for compound 9d (less fluorescent than analogs
7(aee)).
M1 to 1.01
e4 kcal$mol-1 suggesting that this transfer is thermally acces-
sible, as required for the ESIPT mechanism. In the case of compound
d we have characterized two different minimum energy con-
formers M1 and M2, connected by a transition state TS to represent
the Ph-O-H…O]C< proton transfer depicted in Scheme 6. A
detailed inspection of the structure of M1 suggests that distal Ph-O-
Å shows that this process requires less than
ꢀ
2
O at 25 C upon
Fig. 1. Emission spectra of 7(aee) (c ¼ 3x10E-5 mol/L) 1% (v/v) THF/H
3
an excitation from 236 to 262 nm.
9
avoided the ESIPT process. Consequently, we were prompted to
realize the deacetylation reaction of compounds 8 with the aim to
investigate the role of the hydroxyl group in the photoluminescent
behavior of the molecule (Scheme 5).
CH ether group rests close to the region where the proton transfer
3
The fluorescence spectra were recorded in anhydrous
should occur and can stabilize assist the proton transfer process by
dichloromethane (DCM), EtOH and THF/H
2
O mixtures. So while no
H-bonding, as described in Fig. 2. Detail of the optimized structure
of M1 structure of 9d is shown in Fig. 2 where the distances be-
tween the three oxygen atoms and the proton transferred are
shown.
emission was detected in DCM and EtOH, compound 9d was fluo-
rescent in the 1% (v/v) THF-water mixture, however the quantum
yield was lower compared to analogs 7a-e.
In a THF/H
2
O mixture, the fluorescence reappeared never-
This intramolecular proton transfer from M1 to M2 in vacuo has
an energy barrier of 24 kcal$mol-1 (TS) to reach the minimum
energy conformer M2, which is 22 kcal$mol-1 less stable than M1.
This energy profile is too high to be thermally accessible but can be
strongly reduced by the assistance of a water molecule which
provide a Grotthuss-like proton transfer mechanism as
theless with a relative decrease of intensity compared to that
observed for derivatives 7(aee). It is thinkable that the steric hin-
drance caused by the presence of the triazolyl moiety at N
origin of the fluorescence phenomenon. Indeed, the C eC1’ rotation
while being prevented places the hydroxyl group close to the
carbonyl one. In this conformation, the hydrogen of the hydroxyl
group (donor) and the oxygen of the carbonyl group (acceptor)
were able to interact following an intramolecular reversible proton-
transfer causing a sudden change in the luminescence behavior and
a loss of the mesomeric
phenyl ring. (Scheme 6).
A computational study on compounds 7e and 9d in vacuo has
been conducted in order to rationalize the observed fluorescence in
5
is at the
4
Ph-O-H…OHeH/O]C< 4 Ph-O- … HeOH/HeO þ -Cꢁ
Both the distances and the angles of this intermediate structure
are plausible and provide a mechanism to stabilize the excited state
required in the ESIPT process and explains the fluorescence
response of compound 9d described in Table 4. From this model it is
expected that the presence of water in the solvent is required to be
activate the fluorescence, as observed. Also, the longer path justifies
the lower emission quantum yield compared to 7e.
p-electron-delocalization within the
9
d The proton transfer between the two forms involved in ESIPT
mechanisms as described in Schemes 1 (for 7e) and 6 (for 9d) have
been explored by total energy optimization to find possible sta-
tionary molecular structures. For 7e, a single minimum energy
structure M1 has been found and characterized and a short H-bond
between the Ph-O-H and proximal N atom of imino group stabilizes
a planar conformation of this part of the molecule, as expected. A
simple geometry scan to mimic the proximal proton transfer
OeH/N< 4 O- … HeNþ< by reducing the N/H distance from
The larger distance for the proton transfer in 9d explains the
absence of fluorescence in anhydrous media and the lower quan-
tum yield observed for this compound in THF/H O mixtures
2
Fig. 2. Detail of the M1 minimum energy optimized structure of 9d around the groups
Scheme 5. Deacetylation reaction of compound 8d.
involved in the proton transfer proton transfer.
4

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
Table 4
according to the literature using quinine sulfate (
.05 M H SO ) as a standard [31]. The following equation was used
to determine the relative fluorescence quantum yield in solution:
F
¼ 52% in
F
Photophysical data for compound 9d.
0
2
4
Entry
1
Compd
Solvent
l
abs (nm)
l
em (nm)
Stokes (nm)
FF
9d
2
THF/H O
DCM
235
238
238
381
a
a
146
b
b
0,11
c
c
S X X S X S
/A )(F /F )(n /n FF(s)
)2
FF(x) ¼ (A
EtOH
a
b
c
where A is the absorbance (in the range of 0.01e0.1 A.U.), F is the
not applicable.
not determined.
not fluorescent.
area under the emission curve, n is the refractive index of the sol-
ꢀ
vents (at 25 C) used in measurements, and the subscripts s and x
represent standard and unknown, respectively.
compared to 7e. Another mechanism that can be invoked to
interpret fluorescence disappearance in anhydrous DCM and EtOH
can be rationalized in terms of the formation of hydrogen-bonded
dimers (excimers) with an excited-state double proton transfer
4.1. General procedure for the synthesis of BZDs 1e5
4-(2-hydroxyphenyl)-3H-1,5-benzodiazepin-2-one (1) was
prepared according to the literature [26].
(
ESDPT) process [32] that break conjugation of the phenyl ring.
However, this mechanism seems to be effective for fluorescence
quenching only at high concentration of the compounds, which is
not the present case.
4
.1.1. Preparation of 1-prop-2-ynyl-4-(2-hydroxyphenyl)-3H-1,5-
benzodiazepin-2-one (2)
g of benzodiazepinone 1 (4 mmol) and NaH (1 eq) in 40 mL of
1
3
. Conclusion
THF were stirred for 15 min. Then 1.2 eq of propargyl bromide were
added and the mixture was stirred under reflux at 80 C for 3 h.
After filtration, the mixture was purified by chromatography on a
silica column using cyclohexane-ethyl acetate 60:40 as eluent.
ꢀ
In conclusion, in this work, we have described two efficient
regiospecific synthetic routes towards N
1 5
and N -triazolo-1,5-
benzodiazepin-2-ones 7 and 8 using a Cu(I) catalyzed procedure as
the key synthetic step. Compounds 7 and 8 were evaluated for their
photophysical properties giving a set of interesting information
that could potentially make them very interesting probes for
technological applications. The observations resulting from our
studies of the fluorescence behavior of the N-triazolo-1,5-
benzodiazepin-2-ones scaffold bearing a 2-hydroxyphenyl group
at 4-position led us to state that the fact of keeping free the hy-
droxyl group is indispensable for the photoluminescent emission
Expected compounds
2
was obtained in 75% yield.
Mp ¼ 143e145 C. H NMR (300 MHz, DMSO [d ]) ppm: 3.14 (d,
J ¼ 15Hz, 1H), 3.24 (t, J ¼ 3Hz, 1H), 3.36 (d, J ¼ 15Hz, 1H), 4.64e4.67
dd, J ¼ 6Hz, 3Hz, 2H), 6.98e7.05 (m, 2H), 7.36e7.51 (m, 4H),
.74e7.77 (m, 1H), 7.94e7.97 (dd, J ¼ 9Hz, J ¼ 3Hz, 1H), 13.86 (s, 1H);
ꢀ
1
6
d
(
7
13
C NMR (75 MHz, DMSO [d
17.8, 119, 122.2, 125.9, 126.8, 127.3, 130, 133.9, 134.2, 138.2, 161.3,
64.6, 164.8.
6
]) d ppm: 36.4, 37.8, 74.8, 79.5, 117.6,
1
1
(
H
in which the hypothesized mechanism is ESIPT) occurrence in THF/
O mixtures and its absence in anhydrous EtOH and DCM solu-
4
.1.2. Preparation of 4-(2-hydroxyphenyl)-1-methyl-1H ben-zo[b]
2
[
1,4]diazepin-2(3H)-one (3)
tion. On another hand, we have demonstrated that even when both
N1 and N5 are functionalized and as long as the hydroxyl group
remains free, the ESIPT process will take place as a result of the OH/
C]O proton transfer. Results from a computational study of com-
pounds 7e and 9d in vacuo provide further details and arguments
to reinforce this conclusion.
To a solution of compound 1 (1.01 g, 4 mmol) in THF (50 mL),
ꢀ
was added KOH (0.295 g, 1.1 eq) at 0 C. The mixture was stirred for
15 min before the addition of methyl iodide (8 mmol, 1.2 eq). The
ꢀ
mixture was allowed to stir for 4 h at 0 C before filtration through
celite. The solvent was then evaporated off under reduced pressure
and the crude material was purified by column chromatography
(
9
3
cyclohexane/ethylacetate 60:40). Compound 3 was obtained with
4
. Experimental section
ꢀ
1
0% yield. Mp ¼ 172e174 C. H NMR (300 MHz, DMSO [d
6
]) d ppm:
.05 (d, J ¼ 12Hz, 1H) 3.32 (s, 3H), 4.30 (d, J ¼ 15 Hz, 2H) 7.33e7.49
Chemical reagents and solvents were purchased from com-
13
(
m, 4H) 7.56e7.59 (dd, J ¼ 8.4 Hz, J ¼ 1.5 Hz 1H); C NMR (75 MHz,
DMSO [d ]) ppm: 34.8, 37.9, 117.6, 117.8, 118.6, 119, 122.5, 125.3,
26.6, 127.2, 129.9, 134.0, 135.7, 137.7, 161.3, 164.8, 165.3.
mercial suppliers (Merck, Aldrich, and Fluka) and were used as
received without further purification. All reactions involving air
and moisture sensitive reagents were per-formed under Argon
using syringe septum cap technique. All the melting points were
determined in open glass capillaries and are uncorrected. H NMR
and C NMR spectra were recorded in DMSO [d
6
d
1
1
4.1.3. Preparation of 2-(1-methyl-2-oxo-2,3-dihydro-1H-
benzodiazepin-4-yl) phenyl acetate (4)
13
6
] or CDCl
3
on
‘
Brucker Avance 300 MHz’ spectrophotometer with TMS as internal
To a solution of compound 3 (2g, 8 mmol) in 30 mL of acetic
stand-ard in which chemical shifts are expressed in
d
ppm coupling
3
anhydride was added (1 mL, 1.1 eq) of Et N. The mixture was
constants (J) are reported in Hertz (Hz). High-resolution mass
spectra (HRMS) were obtained using an orthogonal acceleration
time-of-flight (oa-TOF) mass spec-trometer equipped with an
allowed to stir for 12 h at room temperature. After removing the
solvent under reduced pressure, the crude material was poured
into distilled water and extracted with dichloromethane. The
þ -
electrospray source and in the positive and negative modes (ESI / ).
4
organic layers were combined and dried over anhydrous MgSO ,
The reactions were monitored by thin-layer chromatography (TLC)
on silica gel G plates in the solvent system cyclohexane/ethyl ace-
tate mixture (6:4) and the spots were visualized with UV light.
UVevisible spectra were obtained using a UV-3100PC Spectro-
photometer. Fluorescence spectroscopic studies were determined
with an instrument Spectrofluorimeter flx-Xenius, with an excita-
then filtered and the filtrate concentrated at reduced pressure. The
crude material was purified by column chromatography on silica
gel (cyclohexane/ethyl acetate) 60:40 Compound 4 was obtained in
ꢀ
1
80% yield. Mp ¼ 168e170 C. H NMR (300 MHz, DMSO [d
6
]) d ppm:
2.83 (s, 3H), 3.10 (s, 1H), 3.44 (s, 3H), 3.96 (s, 1H), 7.16e7.19 (m, 6H),
1
3
7.92 (d, J ¼ 6Hz, 1H); C NMR (75 MHz, DMSO [d
6
])
d
ppm ¼ 20.4,
tion and emission band widths of 10 nm. Fluorescence quantum
34.4, 41.4, 120.9, 122.7, 124.3, 125.3, 125.7, 125.7, 126.5, 129.9, 130.4,
130.9, 134.3, 140.3, 147.9, 159.9, 165.9, 168.5.
ꢀ
yields in THF/H
2
O were measured at 25 C by a relative method
5

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
4
.1.4. Preparation of 2-(5-methyl-4-oxo-1-(prop-2-yn-1-yl)-4,5k-
134.1, 118.0, 124.4, 134.9, 135.3, 135.7, 138.7, 143.5, 162.1, 164.3,
þ
dihydro-1H-benzodiazepin-2-yl) phenyl acetate (5)
165.08;
HRMS
(ESI ):
C
26
H
23
N
5
O
2
calculated
for
[MþNa]þ ¼ 460.1749, obtained for [MþNa] ¼ 460.1763.
þ
To a solution of compound 4 (1g, 3 mmol) in DMF (10 mL), so-
dium hydride NaH (1 eq, 3 mmol, 120 mg) was added. After 15 min,
propargyl bromide was added (1.1 eq, 350 mL). The mixture was
4.3.3. 4-(2-hydroxyphenyl)-1-((1-(o-tolyl)-1H-1,2,3-triazol-4-yl)
ꢀ
stirred at 50 C for 3 h then filtered through celite before removing
methyl)-1H-benzodiazepin-2(3H)-one (7c)
ꢀ
1
ꢀ
3
, 25 C) d:
the solvent under reduced pressure. The crude material was puri-
fied by flash column chromatography on silica gel (cyclo-hexane/
ethyl acetate from 100:0 to 70:30). Compound 5 was obtained in
8
3
Yield 69%, Mp ¼ 177e181 C. H NMR (300 MHz, CDCl
2.08 (s, 3H), 2.95 (d, J ¼ 12 Hz, 1H), 4.25 (d, J ¼ 12Hz, 1H), 4.95 (d,
J ¼ 15Hz, 1H), 5.20 (d, J ¼ 15Hz, 1H), 6.85 (q, 2H), 7.40 (m, 8H), 7.7 (s,
ꢀ
1
13
5% yield, Mp ¼ 173e179 C. H NMR (300 MHz, CDCl
3
):
d
: 1.93 (s,
1H), 7.85 (d, J ¼ 6.9, 1H), 8.10 (d, J ¼ 6.9, 1H); C NMR (75 MHz,
ꢀ
H), 2.54 (t, J ¼ 3Hz, 1H), 3.51 (s, 3H), 4.78 (s, 2H), 6.37 (s, 1H),
CDCl
3
, 25 C)
d: 17.8, 38.2, 44.6, 118.2, 119.1, 123.4, 125.8, 126.0,
1
3
7.06e7.64 (m, 8H); C NMR (75 MHz, CDCl
3
):
d: 166.6, 166, 155.3,
126.8, 126.9, 127.5, 129.3, 129.8 131.4, 134.1, 118.0, 33.4, 135.2, 136.3,
ꢂ
139.9,138.1,131.1, 130.1,129.1,128.4,128.4,128.3,126.4,125.3,125.2,
138.4, 143.5, 162.2, 164.1, 165.0; HRMS (ESI ): C25
H
21
N
5
O
2
calcu-
þ
-
-
122.1, 121.9, 120.9, 113.2, 56, 35.9, 30.9, 22.6. HRMS (ESI ):
lated for [M ꢂ H] ¼ 423.1617, obtained for [M ꢂ H] ¼ 422.1618.
C
21
H
18
N
2
O
3
; Calculated for [MþH]þ ¼ 347.1396, obtained for
þ
[MþH] ¼ 347.1390.
4.3.4. 4-(2-hydroxyphenyl)-1-((1-(2-methoxyphenyl)-1H-1,2,3-
triazol-4-yl)methyl)-1H-benzodiazepin-2(3H)-one (7d)
ꢀ
1
ꢀ
3
, 25 C) d:
4.2. General procedure for the synthesis of 1,3-dipoles (6a-e)
Yield 71%, Mp ¼ 180e189 C. H NMR (300 MHz, CDCl
.05 (d, J ¼ 12Hz, 1H), 3.86 (s, 3H), 4.30 (d, J ¼ 12Hz, 1H), 4.98 (d,
3
13
ꢀ
3
, 25 C)
The arylamine (0.072 mol) was dissolved in a solution of hy-
J ¼ 15Hz,1H), 5.35 (d, J ¼ 15Hz,1H); C NMR (75 MHz, CDCl
drochloric acid-water (1 M) (52 mL) while maintaining stirring. The
d: 38.2, 44.6, 55.9, 118.2, 119.1, 121.1, 123.4, 125.3, 126.0, 126.2, 126.4,
temperature of the reaction should be maintained between 0 and
126.9, 127.6, 129.3, 130.1, 134.1, 112.2, 118.0, 135.2, 138.3, 143.1, 151.1,
ꢀ
ꢂ
5
C. (Solution 1). Sodium nitrite NaNO
2
(0.072 mol) was dissolved
162.2, 164.2, 164.9; HRMS (ESI ): C25
[M ꢂ H] ¼ 438.1566, obtained for [M ꢂ H] ¼ 438.1565.
H
21
-
N
5
O
3
; calculated for
-
in ice-cold water (25.65 g) then poured in small portions into the
solution 1. On the other hand, NaN (0.072 mol) was dissolved in
water (56.7 mL) and added to the reaction mixture and stirred for
h. The precipitate obtained was dissolved with di-chloromethane.
3
4.3.5. 1-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(2-
2
hydroxyphenyl)-1H-benzodiazepin-2(3H)-one (7e)
ꢀ
1
ꢀ
3
, 25 C) d:
The organic layer was washed with water and then dried over
anhydrous sodium sulfate. Finally, the dichloromethane was
removed under reduced pressure. Five different 1,3-dipoles were
obtained with good yields (79e85%). The preparation of these
azides was based on the literature [28].
Yield 84%, Mp ¼ 189e195 C. H NMR (300 MHz, CDCl
3.10 (d, J ¼ 12Hz, 1H), 4.35 (d, J ¼ 12Hz, 1H), 5.10 (d, J ¼ 15Hz, 1H),
13
5.30 (d, J ¼ 15Hz, 1H), 8.08 (s, 1H), 7.10e8.20 (m, 12H); C NMR
ꢀ
(75 MHz, CDCl
3
, 25 C)
d: 38.2, 44.6, 118.2, 119.1, 123.3, 126.1, 126.3,
126.9, 127.2, 127.8, 129.3, 129.5, 130.5, 130.7, 130.8, 118.0, 126.0,
þ
1
C
27.6, 134.1, 134.8, 135.1, 138.4, 143.5, 162.2, 165.0; HRMS (ESI ):
4.3. General procedure for the synthesis of BZDs (7a-e), (8a-e) and
24
H
18ClN
5
O
2
; calculated for [MþH]þ ¼ 444.1227, obtained for
þ
(
9d)
[MþH] ¼ 444.1234.
In a 50 mL flask, dipolarophile 2 (0.300 g, 1 mmol) was intro-
4.4. General procedure for the synthesis of BZDs (8a-e)
duced into 20 mL of dichloromethane and the mixture was stirred
at room temperature for 5 min. One equivalent of azide 6a-e,
triethylamine (2 mL) and 5 mol% Cu (I) copper iodide were added.
The reaction mixture was stirred at room temperature for 8 h. Then
the solvent was evaporated off under reduced pressure and the
crude formed compound was purified by chromatography on silica
gel using cyclohexane/ethyl acetate (60:40) as eluent.
A solution of 5 (0.300 g, 1 mmol) in 20 mL of dichloro-methane
was stirred at room temperature for 5 min. Then, one equivalent of
azide, triethylamine (2 mL) and 5 mol % of Cu (I) copper iodide were
added. The reaction mixture was stirred at room temperature for
8 h. Then the solvent was evaporated off under reduced pressure
and the crude compound was purified by chromatography on silica
gel eluting with cyclohexane/ethyl acetate/methanol (60:30:10).
4.3.1. 1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-4-(2-
hydroxyphenyl)- 1H-benzodiazepin-2(3H)-one (7a)
4.4.1. 2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-methyl-4-
ꢀ
1
ꢀ
Yield 71%, Mp ¼ 186e191 C. H NMR (300 MHz, CDCl
3
, 25 C)
oxo-4,5-dihydro-1H-benzodiazepin-2-yl)phenylacetate (8a)
ꢀ
1
ꢀ
3
, 25 C)
d
ppm: 3.05 (d, J ¼ 12 Hz, 1H) 4.26 (d, J ¼ 12 Hz, 1H), 4.89 (d,
Yield 78%, Mp ¼ 192e197 C. H NMR (300 MHz, CDCl
J ¼ 15 Hz, 1H), 5.15 (d, J ¼ 15 Hz, 1H), 5.48 (d, J ¼ 12 Hz, 1H) 5.50 (d,
J ¼ 12 Hz,1H), 7.10 (q, 2H) 7.35 (m, 9H) 7.60 (s,1H) 7.85 (d, J ¼ 8.1 Hz,
d ppm: 1.78 (s, 3H), 3.50 (s, 3H), 5.32 (s, 2H), 5.56 (s, 2H), 6.40 (s,
1H), 7.20 (m, 9H), 7.30 (s, 1H), 7.04 (s, 2H), 7.18 (s, 1H), 7.55 (d,
3
ꢀ
13
ꢀ
1
3
H) 8.10 (d, J ¼ 8.1, 1H); 1 C NMR (75 MHz, CDCl
3
, 25 C)
d
ppm:
J ¼ 7.5, 1H); C NMR (75 MHz, CDCl
3
, 25 C) d ppm: 22.5, 35.9, 29.6,
8.2, 44.7, 54.2, 118.2, 119.07, 123.3, 126.0, 126.9, 127.5, 128.1, 128.7,
54.5, 113.4, 121.6, 122.2, 125.4, 128.3, 128.7, 129.0, 131.6, 113.0, 121.1,
þ
1
29.1, 129.3, 134.0, 162.3, 118.0, 124.1, 125.9, 134.2, 138.3, 164.0,
124.9, 127.8, 128.5, 131.16, 134.0, 137.5, 155.5, 165.6. HRMS (ESI ):
ꢂ
-
; calculated for [MþH]þ ¼ 480.2036, obtained for
164.9; HRMS (ESI ): C25
H
21
N
5
O
2
calculated for [M ꢂ H] ¼ 422.1617,
C
28
H
25
N
5
O
3
-
þ
obtained for [M ꢂ H] ¼ 422.1621.
[MþH] ¼ 480.1957.
4.3.2. 1-((1-(2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-4-
4.4.2. 2-(5-methyl-4-oxo-1-((1-(o-tolyl)-1H-1,2,3-triazol-4-yl)
(
2-hydroxyphenyl)-1H-benzodiazepin-2(3H)-one (7b)
methyl)-4,5-dihydro-1H-benzodiazepin-2-yl)phenylacetate (8b)
ꢀ
1
3
ꢀ
ꢀ
1
ꢀ
3
, 25 C)
Yield 82%, Mp ¼ 181e188 C. H NMR (300 MHz, CDCl , 25 C)
ppm: 1.18 (s, 6H), 3.00 (d, J ¼ 12 Hz, 1H), 4.20 (d, J ¼ 12Hz, 1H),
.09 (d, J ¼ 15 Hz, 1H), 5.14 (d, J ¼ 15 Hz, 1H), 7.00 (q, 2H), 7.10 (d,
Yield 87%, Mp ¼ 195e199 C. H NMR (300 MHz, CDCl
ppm: 1.90 (s, 3H), 2.26 (s, 3H), 2.40 (s, 3H), 5.40 (d, J ¼ 12Hz, 1H),
5.50 (d, J ¼ 12Hz, 1H), 6.49 (s, 1H), 7.10 (d, J ¼ 6.9, 1H), 7.30 (dd,
¼ 17.4, J 6.9Hz, 4H), 7.45 (m, 5H), 7.55 (d, J ¼ 7.8 Hz, 1H), 7.68 (d,
J ¼ 7.5 Hz, 1H), 8.07 (s, 1H); C NMR (75 MHz, CDCl
25.3, 29.9, 43.3, 70.3, 120.8, 128.3, 129.0, 129.5, 132.7, 133.2, 134.19,
d
d
5
J ¼ 6Hz, 1Hz), 7.45 (m, 5H), 7.55 (s, 1H), 7.80 (d, J ¼ 4.5, 1H), 8.00 (d,
J
1
2
13
ꢀ
13
ꢀ
3
, 25 C) d ppm:
J ¼ 4.5, 1H); C NMR (75 MHz, CDCl
3
, 25 C)
d
ppm: 17.2, 38.2, 44.4,
1
18.2,119.1,123.5,124.2,125.7,126.1,126.9,127.5,128.4,129.3,129.9,
6

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
1
36.2, 136.6, 137.1, 138.8, 127.3, 132.0, 136.2, 140.8, 143.7, 145.3,
means of electronic structure calculations and density functional
theory (DFT) based methods. We have performed B3LYP [33,34]
calculations on structures 9d and 7e in vacuo using standard 6-
þ
150.8, 173.3. HRMS (ESI ):
C
28
H
25
N
5
O
3
;
calculated for
þ
þ
[MþH] ¼ 480.2036, obtained for [MþH] ¼ 480.2047.
31þG* all-electron basis sets [35] as implemented in the GAMESS
4.4.3. 2-(1-((1-(2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)-
package [36,37]. Finally, it can be useful to further interpret the
ESIPT mechanism by inspection of the HOMO-LUMO energy dif-
methyl)-5-methyl-4-oxo-4,5-dihydro-1H-benzodiazepin-2-yl)
phenylacetate (8c)
ferences (
the excited state: for 7e,
structure with NeH bond at 1.01 Å, and for 9d,
D
EH-L) as an approximation of the of the emission from
EH-L ¼ 4.05 eV for M1 and 3.40 eV for the
EH-L ¼ 4.19 eV for
ꢀ
1
ꢀ
Yield 81%, Mp ¼ 191e196 C. H NMR (300 MHz, CDCl
ppm: 1.88 (s, 3H), 1.90 (s, 3H), 2.10 (s, 6H), 5.47 (s, 2H), 6,47 (s, 1H),
.06 (s, 1H), 7.16 (d, J ¼ 7.5Hz, 1H), 7.25 (t, J ¼7.5Hz, J ¼ 5.1 Hz, 4H),
3
, 25 C)
D
d
D
7
7
1
2
M1 and 3.48 eV for M2. Interestingly enough, in both compounds
the expected emission energy at M1 should be significantly lower
than that from the structure with the proton transferred to the N-
atom, as implied by the ESIPT mechanism, with similar values for
7e and 9b as compared to the experimental values (380 nm
(3.26 eV) and 381 nm (3.25 eV), respectively). These results provide
further support to the action of ESIPT mechanism in compound 9d
and the interpretation of the fluorescence in this family of
compounds.
.35 (d, J ¼ 6.9, 2H), 7.50 (d, J ¼ 8.1Hz,1H), 7.60 (d, 7.2Hz,1H), 7.87 (s,
1
3
ꢀ
1
H); C NMR (75 MHz, CDCl , 25 C) d ppm: 17.3, 22.6, 35.9, 62.9,
3
113.5, 114.4, 121.0, 121.7, 122.2, 124.8, 125.4, 128.4, 128.8, 129.2,
130.0, 131.6, 120.0, 135.38, 135.8, 138.0, 143.5, 146.7, 156.1, 166.0,
þ
1
69.7.
HRMS
(ESI ):
C
29
H
27
N
5
O
3
;
calculated
for
þ
þ
[MþH] ¼ 494.2192, obtained for [MþH] ¼ 494.2197.
4
5
.4.4. 2-(1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-
-methyl-4-oxo-4,5-dihydro-1H-benzodiazepin-2-yl)phenylacetate
(
8d)
Declaration of competing interest
ꢀ
1
ꢀ
3
, 25 C)
Yield 68%, Mp ¼ 189e193 C. H NMR (300 MHz, CDCl
d
ppm: 1.95 (s, 3H), 2.15 (s, 3H), 3.86 (s, 3H), 5.43 (s, 2H), 6.44 (s,1H),
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
7
1
.40 (m, 10H), 7.58 (d, J ¼ 1.5Hz, 1H), 7.61 (d, J ¼ 1.5Hz, 1H), 8,45 (s,
13
ꢀ
H); C NMR (75 MHz, CDCl , 25 C) d ppm: 22.7, 36.0, 55.9, 62.6,
3
111.8, 112.3, 113.1, 120.4 121.1, 121.6, 122.1, 124.7, 124.9, 125.2, 125.4,
1
25.7, 128.3, 128.5, 129.0, 129.1, 130.2, 137.4, 150.7, 165.5. HRMS
Acknowledgment
þ
, calculated for [MþH]þ ¼ 496.1985, obtained for
(
[
ESI ): C28
MþH] ¼ 496.1931.
25
H N
5
O
4
þ
This work was partially supported by the University of Mont-
pellier, IBMM (CNRS), ENSCM. The authors are grateful to Professor
Josep Maria Bofill Vill aꢀ and Professor Ib eꢁ rio de P. R. Moreira for
4.4.5. 2-(1-((1-(2-chlorophenyl)-1H-1, 2,3-triazol-4-yl)methyl)-5-
methyl-4-oxo-4,5-dihydro-1H-benzodiazepin-2-yl)phenylacetate
helping with the computational study, and to the Ministry of
Higher Education and Scientific Research of Tunisia for financial
support.
(
8e)
ꢀ
1
ꢀ
3
, 25 C)
Yield 75%, Mp ¼ 193e197 C. H NMR (300 MHz, CDCl
d
ppm: 1.25 (s, 3H), 2.20 (s, 3H), 5.43 (s, 2H), 6.45 (s, 1H), 7.1 (t,
13
J ¼ 7.1Hz, 1H), 7.40 (m, 11H), 8.20 (s, 1H); C NMR (75 MHz, CDCl
3
,
References
ꢀ
2
5 C)
d
ppm: 22.7, 36.0, 62.7, 121.7, 122.1, 125.3, 127.7, 127.9, 130.8,
[
[
[
[
1] A. Agarwal, P.K. Tripathi, S. Tripathi, N.K. Jain, Curr. Drug Targets 9 (2008)
1
30.8,113.1,121.2,124.8,127.2,128.3,129.0,130.3,134.3,137.4,165.5,
þ
; calculated for [MþNa]þ ¼ 522.1309,
895e898.
HRMS (ESI ): C27
Obtained for [MþNa] ¼ 522.1324.
H
22ClN
5
O
3
2] S.H. Chen, K. Jiang, Y. Xiao, X.Y. Cao, M. Arulkumar, Z.Y. Wang, Dyes Pigments
175 (2020) 108157.
3] D. Wu, L. Chen, Q. Xu, X. Chen, J. Yoon, Acc. Chem. Res. 52 (8) (2019)
þ
2
158e2168.
4] Y. Wang, B. Xu, R. Sun, Y.J. Xu, J.F. Ge, J. Mater. Chem. B. 8 (33) (2020)
466e7474.
[5] H.R. Qomi, A. Habibi, S.M. Shahcheragh, Spectrochim. Acta, Part A 174 (2017)
64e170.
4.5. Preparation of compound (9d)
7
A solution of 8d (1 mmol) in a mixture of 10 mL of di-
1
chloromethane and 20 mL of methanol was stirred at room tem-
perature for 5 min. Then (1 mmol,1 eq) of K CO was added and the
[
[
6] D.K. Tiwari, M. Tiwari, T. Jin, Adv. Mater. 1 (5) (2020) 967e987.
7] N.S. Patil, R.B. Dhake, M.I. Ahamed, U. Fegade, J. Fluoresc. 30 (6) (2020)
1295e1330.
2
3
mixture was stirred at room temperature for 4 h. Solvent was
evaporated off under reduced pressure. The crude material was
purified by chromatography on silica gel eluting with cyclohexane/
ethyl acetate (70:30).
[
[
8] D. Udhayakumari, V. Inbaraj, J. Fluoresc. 30 (5) (2020) 1203e1223.
9] F. Ogawa, Y. Karuo, R. Yamazawa, K. Miyanaga, K. Hori, K. Tani, K. Yamada,
Y. Saito, K. Funabiki, A. Tarui, K. Sato, K. Ito, K. Kawai, M. Omote, J. Org. Chem.
85 (2020) 1253e1258.
[
10] R.V. Goreham, Z. Ayed, Z.M. Amin, G. Dobhal, Nano. Futures. 4 (2) (2020)
2001.
11] J. Dai, Y. Hou, J. Wu, B. Shen, Chemistry 5 (36) (2020) 11185e11196.
2
4.5.1. 4-(2-hydroxyphenyl)-5-((1-(2-methoxyphenyl)-1H-1,2,3-
[
triazol-4-yl)methyl)-1-methyl-1H-benzo[b] [1,4]diazepin-2(5H)-
[12] H.A.L. Filipe, M.J. Moreno, L.M.S. Loura, Molecules 25 (15) (2020) 3424.
[
13] L. Mao, Y. Liu, S. Yang, Y. Li, X. Zhang, Y. Wei, Dyes Pigments 162 (2019)
11e623.
one (9d)
1
ꢀ
3
, 25 C)
6
ꢀ
Yield 74%, Mp ¼ 194e198 C. H NMR (300 MHz, CDCl
ppm: 2.00 (s, 3H), 3.29 (s, 3H), 3.32 (s, 3H), 3.77 (s, 2H), 7.45 (m,
, 25 C)
5.14, 56.48, 62.17, 113.46, 113.86, 121.32, 121.40, 122.50, 125.22,
26.06, 126.16, 126.74, 126.98, 127.38, 128.97, 130.78, 131.19, 132.26,
[14] T. Matsumoto, Y. Urano, T. Shoda, H. Kojima, T. Naga-no, Org. Lett. 9 (2007)
d
3375e3377.
ꢀ
[15] W. Lin, L. Long, L. Yuan, Z. Cao, B. Chen, W. Tan, Org. Lett. 10 (2008)
577e5580.
1
3
1
3H), 8.57 (s, 1H), 13C NMR (75 MHz, CDCl
3
d ppm: 26.81,
5
[16] Shunsuke Sasaki, P.C. Gregor, Drummen and gen-ichi konishi, J. Mater. Chem.
C 4 (2016) 2731.
þ
1
34.93.
HRMS
(ESI ):
C
26
23
H N
5
O
3
;
calculated
for
[17] C. Ma, F. Zeng, L. Huang, S. Wu, J. Phys. Chem. B 115 (2011) 874e882.
[18] M. Oh-e, A. Nagasawa, Organometallics 39 (22) (2020) 3951e3960.
þ
þ
[MþNa] ¼ 476.1699, Obtained for [MþNa] ¼ 476.1721.
[
19] Y. Sato, A.N. Hern ꢁa ndez, L.D. Gillespie, D. Valete, Chem. Phys. 539 (2020)
10940.
[20] J. Zhao, S. Ji, Y. Chen, H. Guo, P. Yang, Phys. Chem. Chem. Phys. 14 (2012)
803e8817.
1
5
. Computational studies
8
[
[
21] A. Nsira, A. Karoui, R. Gharbi, M. Msaddek, J. Chem. Res. 36 (2012) 152e156.
The origin of the unexpected fluorescence response of com-
pound 9d compared to compounds 7a-e has been investigated by
22] S. Chekir, M. Debbabi, A. Regazzetti, D. Darg eꢀ re, O. Lapr eꢁ vote, H.B. Jannet,
R. Gharbi, Bioorg. Chem. 80 (2018) 189e194.
7

C. Ismail, H. Mtiraoui, J.-Y. Winum et al.
Tetrahedron 86 (2021) 132078
[
[
[
[
[
23] Z. Jaafar, S. Chniti, A.B. Sassi, H. Dziri, S. Marque, M. Lecouvey, R. Gharbi,
M. Msaddek, J. Mol. Struct. 1195 (2019) 689e701.
747e757.
[30] V.R. Kamalraj, S. Senthil, P. Kannan, J. Mol. Struct. 892 (1e3) (2008) 210e215.
[31] A.M. Brouwer, Pure Appl. Chem. 83 (12) (2011) 2213e2228.
[32] S. Hisham, H.A. Tajuddin, C.F. Chee, Z.A. Hasan, Z. Abdullah, J. Lumin. 208
(2019) 245e252.
24] W. Abdallah, M. Znati, A. Regazzetti, D. Darg eꢀ re, O. Lapr eꢁ vote, H. Ben Jannet,
R. Gharbi, Phosphorus, sulfur, Silicon. Relat. Elem. 192 (2017) 835e844.
25] H. Mtiraoui, R. Gharbi, M. Msaddek, Y. Bretonni eꢀ re, C. Andraud, C. Sabot,
P.Y. Renard, J. Org. Chem. 81 (2016) 4720e4727.
26] M. Hamdi, O. Grech, R. Sakellariou, V. Sp eꢁ zale, J. Heterocycl. Chem. 31 (2)
[33] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[34] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[35] P.C. Hariharan, J.A. Pople, Theor. Chim. Acta 28 (1973) 213e222.
[36] K. Ishimura, S.N.T.C. Acc, L.E. McMurchie, E.R. Davidson, J. Rys, J. Comput.
Chem. 14 (1993) 1347e1363.
(
1994) 509e511.
27] Q.J. Meisner, J.V. Accardo, G. Hu, R.J. Clark, D.E. Jiang, L.J. Zhu, Phys. Chem. 122
11) (2018) 2956e2973.
(
[28] M. Kaya, E. Mente s¸ e, J. Heterocycl. Chem. 57 (4) (2020) 1714e1719.
[37] M.S. Gordon, M.W. Schmidt, Elsevier, 2005, pp. 1167e1189.
[29] H. Mtiraoui, A. Nsira, M. Msaddek, P.Y. Renard, C.C.R. Sabot, Chim 20 (2017)
8