Synthesis, Crystal Structure, and Photophysical Properties of 4-(4-(Dimethylamino)phenyl)-6-phenylpyrimidin-2-amine

Article abstract of DOI:10.1016/j.molstruc.2020.129340

The pyrimidine core is present in a wide variety of compounds that show interesting fluorescent properties and have been used as pigments and dyes. In this research, we synthesized 4-(4-(dimethylamino)phenyl)-6-phenylpyrimidin-2-amine (compound 9) from ch

Full text of DOI:10.1016/j.molstruc.2020.129340

Journal of Molecular Structure 1226 (2021) 129340
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis, Crystal Structure, and Photophysical Properties of
4-(4-(Dimethylamino)phenyl)-6-phenylpyrimidin-2-amine
Marco Mellado∗, Rafaela Sariego-Kluge, Franco Valdés-Navarro, Rodrigo Sánchez-González,
Mauricio Fuentealba, Manuel A. Bravo, Luis F. Aguilar∗
Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso Av. Universidad #330, Curauma, Valparaíso, Chile
a r t i c l e i n f o
a b s t r a c t
Article history:
The pyrimidine core is present in
a wide variety of compounds that show interesting fluores-
Received 19 August 2020
Revised 22 September 2020
Accepted 24 September 2020
Available online 28 September 2020
cent properties and have been used as pigments and dyes. In this research, we synthesized 4-(4-
(dimethylamino)phenyl)-6-phenylpyrimidin-2-amine (compound 9) from chalcone (8) with 45% yield. We
obtained monocrystals of 9 by slow evaporation of dichloromethane as a solvent. Additionally, we mea-
sured the photophysical properties of compound 9, and its absorption wavelength (λabs), molar absorption
coefficient (ε), excitation wavelength (λexc) and emission wavelength (λem), as well as Stokes shift (ꢀλ),
increase with increasing solvent polarity. These properties are all related to the stabilization of the ex-
cited state by the solvent. On the other hand, the quantum yields (ꢁ values) in toluene and CH2Cl2 were
notable greater than those in other solvents due to their high optical density (OD) and the decrease in
the loss of fluorescence by non-radiative processes
Keywords:
Chalcone
2-amino-pyrimidin
Crystal structure
Absorption properties
Emission properties
© 2020 Elsevier B.V. All rights reserved.
1. Introduction
82% [11]. Additionally, 2-aminopyrimidines can be synthesized by
the condensation of chalcones with guanidine. For example, Adsul
For more than a century, nitrogenous heterocycles have at-
tracted attention in various branches of the chemical sciences due
to their wide range of properties useful to medical chemistry as
well as material science [1,2]. For example, the pyrimidine core
is present in nature as part of the nitrogenous bases that make
up DNA [3,4]. In this context, the 2-aminopyrimidine core has at-
tracted great interest from medicinal chemists due to its pharma-
cological activities [5]. Indeed, many researchers have described
the anti-inflammatory, anticancer, antimicrobial, antiviral, and anti-
HIV activities of molecular systems that contain this fragment [6-
9]. In addition, compounds possessing the 2-aminopyridine frag-
ment exhibit interesting fluorescent and electrochemical proper-
ties [10], and have been used in fabric dyes and photovoltaic cells
[11,12]. Their properties suggest they could be applicable in the de-
sign of sensors as well as in the field of materials science.
et al. obtained derivative 4 (see Fig. 1) using a heteroaryl-chalcone
as a precursor in 80% yield under reflux conditions in an alkaline
medium; [12] Khan et al. obtained bis-2-aminopyrimidine deriva-
tive 5 using ferrocenyl-chalcone as a starting material in 76% yield
under microwave irradiation [13].
Due to the pharmacological importance of these compounds,
as well as their potential uses in the fields of materials science
and fluorescent sensors, in this work, we report the structural and
photophysical characterization of 4-(4-(dimethylamino)phenyl)-6-
phenylpyrimidin-2-amine (compound 9) synthesized from the con-
densation of guanidine and (2E)-3-[4-(dimethylamino)phenyl]-1-
phenyl-prop-2-en-1-one (compound 8, see Scheme 1).
2. Experimental
2.1. Instrumentation
From a synthetic point of view, 2-aminopyrimidines can be ob-
tained by condensation reactions between α,β-unsaturated car-
bonyls and guanidine [10]. Indeed, the intermediates in the synthe-
sis of meridianin alkaloids C (1), D (2) and E (3) (see Fig. 1) were
synthesized by the previously mentioned reaction in yields of 72-
Melting points were measured using a Fischer Scientific appa-
ratus (Pittsburgh, PA, USA). Infrared spectra were recorded using
a Jasco FT/IR 4600 (Tokyo, Japan). The recorded range of the IR
spectra was 400 cm−1 to 4000 cm−1 using a KBr disk. 1H NMR,
13C NMR, 2D-HSQC and 2D-HMBC spectra were recorded using a
Bruker Avance 400 Digital NMR spectrometer (Berlin, Germany)
operating at 400.13 MHz for 1H and 100.6 MHz for 13C. Chemical
shifts are reported in δ (ppm downfield from the TMS resonance),
∗
Corresponding authors.
E-mail addresses: marco.mellado@pucv.cl (M. Mellado), luis.aguilar@pucv.cl (L.F.
Aguilar).
https://doi.org/10.1016/j.molstruc.2020.129340
0022-2860/© 2020 Elsevier B.V. All rights reserved.

M. Mellado, R. Sariego-Kluge, F. Valdés-Navarro et al.
Journal of Molecular Structure 1226 (2021) 129340
Fig. 1. 2-Aminopyrimidine derivatives obtained from α,β-unsaturated carbonyl and guanidine condensations.
Scheme 1. Synthesis of 2-amino pyrimidine. Reagents and conditions: a. Claisen-Schmidt reaction, NaOH-saturated methanol, stirred for 48h at r.t. (82% yield). b. Guanidine
hydrochloride, NaOH-saturated methanol, stirred for 8 h at reflux (45% yield).
112.3 (2xCH), 110.9 (C), 40.4 ((CH3)2N). 1H NMR, 13C NMR, and MS
and coupling constants (J) are given in Hz. GC-MS analyses were
carried out using an Agilent Technologies 6890 instrument (Santa
Clara, CA, USA) with an automatic ALS and HP MD 5973 mass de-
tector in splitless mode. Absorption spectra were recorded on a
Shimadzu UV-mini-1240 UV-Vis spectrophotometer (Kyoto, Japan).
All steady-state fluorescence measurements were performed on an
ISS K2 Multifrequency Phase Fluorometer (Champaign, IL, USA).
analysis results are consistent with our previous report [14,15].
2.3.2. Amino pyrimidine synthesis
To a dry, 100-mL round-bottomed flask were added chalcone
8 (250 mg, 1.00 mmol) and guanidine hydrochloride (190 mg,
2.0 mmol). Both reagents were dissolved in methanol (10 mL), a
NaOH-saturated methanol solution was added dropwise (10 mL),
and the mixture was stirred for 8 h at reflux. The reaction was
ended by the addition of 5% HCl solution until pH ~ 7, and the mix-
ture was extracted with CH2Cl2 (3 × 30 mL). The organic layer was
dried with Na2SO4, filtered, and separated by column chromatogra-
phy using hexane/EtOAc mixtures of increasing polarity, affording
compound 9.
2.2. Chemicals
Acetophenone (6), 4-dimethylamino benzaldehyde (7),
guanidine hydrochloride (8), dimethylsulfoxide (DMSO), hep-
tane (C7H16 ), toluene, tetrahydrofuran (THF), dioxane, acetone
(Me2CO), dimethylformamide (DMF), HEPES sodium salt HCl,
NaOH, H2SO4, were purchased from Sigma-Aldrich (St. Louis, MO,
USA). Methanol, ethanol, hexane, dichloromethane (CH2Cl2), ethyl
acetate and acetonitrile (MeCN) were purchased from J.T. Baker
(Radnor, PA, USA).
4-(4-(Dimethylamino)
phenyl)-6-phenylpyrimidin-2-amine
(9)
Yellow solid (45% yield). MP: 156-164°C. IR: νmax/cm−1 3483,
3279, 3064, 2800, 1613, 1568, 1565, 1531, 1371, 815, 769, 566; 1H
NMR (400 MHz, CDCl3): δ 7.96 (2H, m, 2x CHAr), 7.94 (2H, d,
J = 9.0 Hz, 2x CHAr), 7.40 (3H, m, 3x CHAr), 7.18 (1H, s, CHAr),
6.70 (2H, d, J = 9.0 Hz, 2x CHAr), 5.04 (2H, br s, NH2), 2.97 (6H, s,
(CH3)2N); 13C NMR (100 MHz, CDCl3): δ 166.0 (C), 165.5 (C), 163.5
(C), 152.1 (C), 138.3 (C), 130.1 (C), 128.7 (2xCH), 128.3 (2xCH), 127.1
(2xCH), 124.8 (C), 111.8 (2xCH), 102.9 (C), 40.2 ((CH3)2N). IR, 1H
NMR and MS analysis results are consistent with previous report
[16-18].
2.3. Synthetic procedure
2.3.1. Chalcone synthesis
To a dry, 100-mL round-bottomed flask were added acetophe-
none 6 (200 mg, 1.66 mmol) and 4-dimethylamino benzaldehyde
7 (247 mg, 1.66 mmol). Both reagents were dissolved in methanol
(10 mL), a NaOH-saturated methanol solution was added dropwise
(10 mL), and the mixture was stirred for 48 h. The reaction was
ended by the addition of 5% HCl solution until pH ~ 7, and the mix-
ture was extracted with EtOAc (3 × 30 mL). The organic layer was
dried with Na2SO4, filtered, and separated by column chromatogra-
phy using hexane/EtOAc mixtures of increasing polarity, affording
compound 8.
2.4. X-ray crystallographic study
A single crystal of compound 9 was mounted on a MiTeGen Mi-
croMount in a random orientation. The diffraction data were col-
lected at 170(2) K on a Bruker D8 QUEST diffractometer equipped
with a two-dimensional CMOS Photon100 detector using graphite
(2E)-3-[4-(Dimethylamino)phenyl]-one-phenyl-prop-2-in-
˚
one-one (8)
monochromated Mo-Kα radiation (λ = 0.71073 A). The diffraction
Orange solid (82% yield). MP: 109-111 C. IR: νmax/cm− 1 3062,
2966, 1644, 1564, 1532, 1486, 1460, 1228, 1167; 1H NMR (400
MHz, CDCl3): δ 7.99 (2H, d, J = 7.6 Hz, 2x CHAr), 7.79 (1H, d,
J = 15.5 Hz, CHtrans), 7.55 (2H, d, J = 8.6 Hz, 2x CHAr), 7.54 (1H, m,
CHAr), 7.48 (2H, d, J = 7.6 Hz, 2x CHAr), 7.34 (1H, d, J = 15.5 Hz,
CHtrans), 6.73 (2H, d, J = 8.6 Hz, 2x CHAr), 3.03 (6H, s, (CH3)2N);
13C NMR (100 MHz, CDCl3): δ 190.7 (C), 145.7 (CH + C), 138.9 (C),
132.2 (2xCH), 130.4 (CH), 128.4 (2xCH), 128.3 (2xCH), 117.2 (CH),
frames were integrated using the APEX3 package [19]. The struc-
ture was solved by dual space methods using the SHELXT program
[20] in Olex2 software [21]. The structure was refined with full-
matrix least-squares methods based on F2 (SHELXL-2018/1) [22].
All non-hydrogen atoms were refined with anisotropic atomic dis-
placement parameters. Except for hydrogen atoms linked to ni-
trogen atoms in the amino group, which were introduced in the
structural model through Fourier difference map analysis, the H
2

M. Mellado, R. Sariego-Kluge, F. Valdés-Navarro et al.
Journal of Molecular Structure 1226 (2021) 129340
Table 1
atoms were placed in their geometrically idealized positions and
constrained to ride on their parent atoms. A summary of the crys-
tal data, the collection parameters and the refinement is presented
in Table S1, and additional crystallographic details are in the CIF
files. ORTEP diagrams were drawn using Olex2 software [21]. The
crystal structure was refined as a racemic twin with a 0.48/0.52
ratio.
˚
Selected bond distances (A) and angles (°) for compound
9.
˚
Bond distances (A)
Bond angles (°)
N2-C9
N2-C16
N3-C16
N3-C7
C7-C8
1.341(3)
1.336(3)
1.342(3)
1.343(3)
1.384(3)
1.395(3)
1.363(3)
C16-N2-C9
C16-N3-C7
N3-C7-C8
C7-C8-C9
116.62(19)
115.79(19)
121.4(2)
118.4(2)
120.5(2)
116.8(2)
127.0(2)
116.1(2)
N2-C9-C8
N2-C16-N4
N2-C16-N3
N3-C16-N4
C8-C9
2.5. Photophysical study
N4-C16
Fluorescence excitation and emission spectra were obtained us-
ing a xenon arc lamp as the light source. Fluorescence spectra
were measured at 90° in an L-format using single photon count-
ing mode. Data were acquired and analysed by VinciTM software,
according our previous report [23].
Table 2
Hydrogen-bonding interaction parameters for compound 9.
˚
˚
˚
DHꢀꢀꢀTO
DH (A)
DꢀꢀꢀA (A)
HꢀꢀꢀA (A)
ࢬDHꢀꢀꢀA (°)
The relative quantum yield (ꢁ) was determined using fluores-
cein as a standard (0.1 M NaOH at 22°C, ꢁ = 0.95, λex = 496 nm)
[24]. Eq. 1 was used to calculate the quantum yield [25].
N4-H4AꢀꢀꢀN3i
C2-H2ꢀꢀꢀN3
0.90(3)
0.93
2.28(3)
2.48
3.045(3)
2.792(3)
2.795(3)
143(2)
100
C15-H15ꢀꢀꢀN2
0.93
2.47
101
Symmetry code: i1/2-x, + y, -1/2 + z.
Fu As n2
ꢁ =
x
x
u xꢁs
s
(1)
F
Au n2
s
where the subscripts u and s indicate the test and standard, re-
spectively. ꢁ is the quantum yield, A is the absorbance at the ex-
citation wavelength, F is the integrated emission spectrum, and n
is the refractive index of the solvent.
2.6. Computational Details
The compound 9 was optimized using DFT-B3LYP-6-31G (d,p)
level of theory calculations, performed with Gaussian 09 soft-
ware [26]. and the optimized structure was verified by frequency
calculations (obtaining no imaginary frequencies) in the gaseous
phase. The molecular orbitals HOMO and LUMO were plotted with
Isovalue= 0.02 and density = 0.0004; while the electrostatic po-
tential map was plotted, using SCF density matrix with coarse grid
and isovalue = 0.0004.
Fig. 2. Molecular structure of 9 with the atom numbering scheme. The thermal
ellipsoids are drawn at 30% probability.
3. Results and discussion
The aromatization of the 2-pyrimidine ring was corroborated
by the absence of 1H-NMR signals at δ~ 4.00 ppm and δ ~ 2.50
ppm, characteristic of the products of 1,2 and 1,4 addition to α,β-
unsaturated carbonyls, as shown by some derivatives obtained us-
ing guanidine analogues such as urea and thiourea [27,28].
3.1. Chemical
4-(4-(dimethylamino)phenyl)-6-phenylpyrimidin-2-amine
(9)
was obtained by the reaction sequence shown in Scheme 1. The
synthesis of chalcone 8 was carried out in an alkaline medium,
and an orange-coloured solid was obtained after purification of
the reaction mixture. The infrared spectrum shows a signal charac-
teristic of a conjugated carbonyl moiety (υ = 1644 cm−1), typical
of chalcones. The 1H-NMR spectrum shows two low-field doublets
(δ = 7.79 and 7.34 ppm) with coupling constants J = 15.5 Hz,
typical of trans chalcone hydrogens. All the 1H-NMR and 13C-NMR
signals are consistent with previous reports from our research
group [14,15].
3.2. X-ray Crystalline and Molecular Structure
Crystals suitable for X-ray crystallography were obtained by
slow evaporation of saturated solutions of compound
9 in
dichloromethane. 9 crystallizes in the centrosymmetric orthorhom-
bic Aea2 space group with one molecule per asymmetric unit. The
experimental and crystallographic data for compound 9 are pre-
sented in Table S1. Selected bond lengths and angles are summa-
rized in Table 1, and hydrogen-bond interactions are exhibited in
Table 2. An ORTEP diagram of compound 9 along with the atom
numbering scheme is shown in Fig. 2.
Guanidine hydrochloride was then mixed with chalcone 8 in
an alkaline environment to form 2-aminopyrimidine derivative 9,
which was obtained as a pale-yellow solid after purification of the
reaction mixture. The infrared spectrum shows an absorption band
at ν= 3483 cm−1 corresponding to the stretch of the N-H bond of
the -NH2 fragment linked to the pyrimidine core; additionally, the
absorption band at ν= 1644 cm−1, characteristic of the carbonyl
group of chalcone 8, is not present. The 1H-NMR spectrum shows
no doublets (δ = 7.79 and 7.34 ppm) corresponding to the trans
hydrogens of the chalcone. In addition, a broad singlet is present
at δ = 5.02 ppm, which corresponds to the two hydrogens on
the amine at position 2 of the pyrimidine core of α,β-unsaturated
(δ = 190.7 ppm) chalcone 8.
The formation and aromatization of the 2-pyrimidinamine
group were confirmed by the following features: (i) the C7-N3, C9-
N2, C16-N3 and C16-N2 bond lengths are between the C-N single
bond and C=N double bond lengths [29], (ii) no residual electron
densities are observed around N2 and N3, indicating the absence of
hydrogen atoms linked to these atoms, and (iii) the bond distances
of the 2-pyrimidinamine are in full agreement with the mean bond
lengths in 4,6-diphenyl-2-pyrimidinamine analogous (see Table 2)
[30-35].
3

M. Mellado, R. Sariego-Kluge, F. Valdés-Navarro et al.
Journal of Molecular Structure 1226 (2021) 129340
Table 3
Summary
of
the
Photophysical
Properties
of
4-(4-(dimethylamino)phenyl)-6-
phenylpyrimidin-2-amine (9).
Solvent
SDC1
λ abs.2
Log10ε3
λexc.4
λem.5
ꢀλ6
ꢁ7
n8
Heptane
Toluene
CH2Cl2
THF
0.0
2.4
3.1
4.0
4.8
5.1
5.8
6.4
5.1
5.2
9.0
355
362
364
364
364
363
364
365
365
364
364
2.542
3.431
3.652
3.382
3.499
3.514
3.461
3.463
3.444
3.373
3.584
349
367
366
364
365
363
375
370
368
366
375
377
413
455
451
439
470
489
484
491
489
544
28
0.016
0.964
0.900
0.067
0.038
0.085
0.039
0.422
0.002
1.387
1.496
1.424
1.407
1.422
1.359
1.344
1.430
1.329
1.360
1.340
46
89
87
Dioxane
Acetone
ACN
74
107
114
114
123
123
169
DMF
MeOH
EtOH
0.019
†
H2O
1
SDC = Solvent’s Dielectric Constant.
2
3
4
5
6
7
8
†
λ
abs. = Absorption wavelength (nm).
∗
∗
ε = Molar extinction coefficient (L Mol−1 cm−1).
λ
λ
exc. = Excitation wavelength (nm).
em. = Emission wavelength (nm).
ꢀλ = Stokes shift (nm).
ꢁ = Quantum yield.
n = Refractive index.
Quantum yield 4.0 × 10−5
.
In this structure, two phenyl groups are attached to the
pyrimidine. The dihedral angles between the pyrimidinamine ring
and the phenyl and 4-(dimethylamino)phenyl are 17.76(8)° and
11.01(8)°, respectively. These rotational angles are consistent with
the two weak C-H•••N interactions connecting the C-H from the
phenyl rings and the nitrogen atoms of the pyrimidinamine ring
(see Table 3).
reported; however, this phenomenon may be associated with the
decrease in energy and stabilization of the excited state of com-
pound 9 in polar solvents, similar to what has been reported for
variations in λem and the polarity of the solvent [24]. In this con-
text, when correlating the dielectric constant of each solvents and
the excitation wavelength, it can be seen that there is a slight cor-
relation between the two properties (r2 = 0.691).
One intermolecular hydrogen bond is observed for two com-
pounds between the amino group and a nitrogen in the pyrimidine
ring, N4-H4A•••N3 (1/2-x, + y, -1/2 + z). The crystal structure is
stabilized by this network of intermolecular hydrogen bonds, gen-
erating infinite zig-zag chains along the c-axis (see Fig. 3).
The emission wavelength (λem) of compound 9 varies depend-
ing on the solvent in which this property is measured (see Fig. 4B);
for example, in heptane, λem = 377 nm, while in DMF, λem = 484
nm (polar aprotic solvent, see Table 4, Fig. 4B) and in water,
λem = 544 nm (polar protic solvent, Table 3, Fig. 4B, Supple-
mentary Material Fig. S8). These results are consistent with the
bathochromic shift in the emission wavelength due to the stabi-
lization of the excited state by the polar solvent [24]. There is a
strong correlation between the dielectric constant of each solvent
and λem (r2 = 0.900), consistent with what was previously men-
tioned.
3.3. Photophysical measurements
Due to the interesting photophysical properties of compounds
containing the 2-aminopyrimidine fragment, as well as its po-
tential uses in fluorescent sensors, [36] the photophysical prop-
erties of 4-(4-(dimethylamino)phenyl)-6-phenylpyrimidin-2-amine
(9) were measured. For this, a 10 mM stock solution of 9 was pre-
pared in DMSO. Then, compound 9 was dissolved in different sol-
vents to measure the absorption and molecular emission proper-
ties. The results are summarized in Table 4.
The results presented in Table 4 show that in nonpolar solvents,
ꢀλ is short (heptane = 28 nm), while in polar protic solvents, ꢀλ
is long (water = 169 nm), and this trend is similar to those in other
reports [39,40]. There is a strong correlation between the dielectric
constant of each solvent and ꢀλ (r2 = 0.872), which is mainly re-
lated to the λem red shift of compound 9 (see Table 4).
The absorption wavelengths (λabs values) of compound
9
The quantum yield of compound 9 was measured in differ-
ent solvents using Eq. 1 and fluorescein as a standard. Consid-
ering heptane as the reference solvent (ꢁ = 0.016, see Table 4),
when using a slightly more polar solvent such as toluene, a notable
increase in the quantum yield was observed (ꢁ = 0.964); how-
ever, when using a more polar solvent such as dichloromethane
and acetonitrile, the increase in the quantum yield is smaller,
ꢁ = 0.900 and ꢁ = 0.422, respectively. Interestingly, there is no
correlation between the dielectric constant of the solvent and ꢁ
(r2 = 0.066). However, a slight correlation is present between ꢁ
and the refractive index of each solvent (r2 = 0.615); therefore, the
quantum yield could be related to the optical density of the dif-
ferent solvents and not favouring non-radiative de-excitation pro-
cesses.
were determined in different solvents and at different concentra-
tions (20 - 100 μM). Considering heptane as a reference solvent
(SDC = 0.0, λabs = 355 nm), a bathochromic shift in the absorp-
tion maximum occurred in more polar solvents such as THF, DMF,
and water (see Table 4, Fig. 4A). These results are associated with
the different solute/solvent interactions that stabilize the excited
state of compound 9 [37].
The ε of compound 9 was evaluated in different solvents (see
Table 4). Comparing the ε in heptane (Log10ε = 2.542) with those
recorded in the other solvents (shown in Table 4) shows that these
values increase by ~1 order of magnitude. This increase in ε could
be related to the stability provided by polar solvents, since the
light absorption capacity of a molecule depends on the dipole mo-
ment of the transition state [38].
Fluorescent compounds with a high quantum yield value, are a
good platform to chemosensor development due to their efficient
emission of photons compared to absorption of photons [24]. Com-
pound 9 showed a high quantum yield value in solvents with low
On the other hand, the excitation wavelength (λexc) of com-
pound 9 shows a bathochromic shift considering heptane as the
reference, from λexc = 349 nm to λexc = 375 nm (see Table 4). The
variation in λexc in solvents with different polarities has not been
4

M. Mellado, R. Sariego-Kluge, F. Valdés-Navarro et al.
Journal of Molecular Structure 1226 (2021) 129340
Fig. 3. Intermolecular hydrogen bonding interactions. Symmetry code: i(1/2-x, + y, -1/2 + z).
Fig. 4. Absorption and emission spectra of compound 9 in different solvents. A. UV-Vis spectra at a concentration of 100 μM B. Fluorescence spectra at a concentration of
20 μM. ∗Fluorescence spectra recorded in DMF and THF were diluted 10 times (2.0 μM).
polarity (Toluene, and CH2Cl2, see Table 3). However, these sol-
vents are incompatible with aqueous systems. Thus, their applica-
tion as chemosensor in this type of system is unfeasible. More-
over, its quantum yield value in the polar solvents such as DMF is
relatively high (ꢁ= 0.422). This solvent easily mixes with water.
Therefore, the influences of water content in DMF, as well as the
influence of the pH value in the emission properties of compound
9 were measured (see Fig. 5 and Supplementary Material Fig. S10).
Compound 9 showed a systematic fluorescence quenching in
relationship with an increase of water content (see Fig. 5A). The
highest emission intensity of compound 9 was recorded with the
organic solvent (DMF). However, when water was added (10%), the
emission intensity was quenched, resulting in a low quantum yield
value of compound 9 in this case (see Table 3). In this context,
the ratio DMF: H2O 6:4 mixture has similar emission intensity
than any another mixture with higher water content (see Fig. 5A).
Due to this, the influence of the pH value on emission proper-
ties was evaluated, using the water-DMF mixture previously men-
tioned. The results are shown in Fig. 5B. In this figure, at pH> 5.0
no significant changes in emission intensity are observed. However,
5

M. Mellado, R. Sariego-Kluge, F. Valdés-Navarro et al.
Journal of Molecular Structure 1226 (2021) 129340
Fig. 5. Influence of water content and pH value in the emission properties of compound 9. A. Influence of water amount. B. Influence of pH. C8= 10 μM, Buffer HEPES 100
mM pH adjusted to 1.0-14.0.
Fig. 6. Frontier Molecular orbital and electrostatic potential map of compound 8. A. HOMO. B. LUMO. C. ESP.
at pH <5.0 a decrease in emission intensity is observed. Therefore,
from a molecular structure point of view, the nitrogen atoms of
compound 9 could be interacting with the acidic media, causing
the previously mentioned effect. To confirm this, the electrostatic
potential map (MEP), and the frontier molecular orbitals of com-
pound 9 were plotted (see Fig. 6). We found that a nitrogen atom
opposite to Ph-NMe2 ring could be bonding to the hydrogen of the
acidic media, due to high negative charge density (see red color
in Fig. 6C). Moreover, regarding the three nitrogen atoms, the ni-
trogen atom opposite to Ph-NMe2 ring showed a high electronic
density in HOMO (see Fig. 6A). These results are according to the
intermolecular hydrogen bonding of X-Ray results showed in Fig. 3.
CRediT authorship contribution statement
Marco Mellado: Conceptualization, Methodology, Software,
Validation, Formal analysis, Investigation, Formal analysis, Re-
sources, Funding acquisition, Resources, Writing - review & edit-
ing. Rafaela Sariego-Kluge: Investigation. Franco Valdés-Navarro:
Investigation. Rodrigo Sánchez-González: Investigation. Mauricio
Fuentealba: Investigation, Resources. Manuel A. Bravo: Super-
vision, Writing - review & editing. Luis F. Aguilar: Resources,
Methodology, Supervision, Writing - review & editing.
Acknowledgements
The authors thank to Agencia Nacional de Investigación y Desar-
rollo (ANID) and Vicerrectoría de Investigación y Estudios Avanza-
dos of Pontificia Universidad Católica de Valparaíso (VRIEA-PUCV).
This work was supported by the ANID [Fondecyt Postdoctoral grant
3180408]; and VRIEA-PUCV [37.0/2017]
4. Conclusions
4-(4-(dimethylamino)phenyl)-6-phenylpyrimidin-2-amine
(9)
was synthesized from chalcone 8 in 45% yield. Single crystals of
compound 9 were obtained and studied.
Additionally, the photophysical properties of compound 9 were
measured, and the λabs, ε, λexc, λem, and ꢀλ values increase when
increasing the polarity of the solvent due to the stabilization of the
excited electronic state. On the other hand, ꢁ increases in solvents
with high optical density (toluene and CH2Cl2), which could be re-
lated to the decrease in the loss of fluorescence by nonradiative
processes. The photophysical properties are promissory to design
of chemosensor based in the structure of compound 9.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2020.129340.
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We declare that we have no conflicts of interest to this work.
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