Solubility of 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine in tetrahydrofuran and alcohols between 288.15 K and 318.15 K

Article abstract of DOI:10.1016/j.molliq.2020.113170

2,4-diamino-6-(4-pyridyl)-1,3,5-triazine (DAPT) was synthesized and analyzed by nuclear magnetic resonance and Fourier transform infrared spectroscopy, thermogravimetric and elemental analysis techniques as well as by high-resolution transmission electron

Full text of DOI:10.1016/j.molliq.2020.113170

Journal Pre-proof
Solubility
of
2,4-diamino-6-(4-pyridyl)-1,3,5-triazine
in
tetrahydrofuran and alcohols between 288.15K and 318.15K
Xianzhao Shao, Maifang Zuo, Changchun Zhao, Wei Wang,
Zhizhou Li
PII:
S0167-7322(20)30740-6
DOI:
https://doi.org/10.1016/j.molliq.2020.113170
MOLLIQ 113170
Reference:
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
4 February 2020
5 April 2020
15 April 2020
Please cite this article as: X. Shao, M. Zuo, C. Zhao, et al., Solubility of
2,4-diamino-6-(4-pyridyl)-1,3,5-triazine in tetrahydrofuran and alcohols between
288.15K and 318.15K, Journal of Molecular Liquids (2020), https://doi.org/10.1016/
j.molliq.2020.113170
This is a PDF file of an article that has undergone enhancements after acceptance, such
as the addition of a cover page and metadata, and formatting for readability, but it is
not yet the definitive version of record. This version will undergo additional copyediting,
typesetting and review before it is published in its final form, but we are providing this
version to give early visibility of the article. Please note that, during the production
process, errors may be discovered which could affect the content, and all legal disclaimers
that apply to the journal pertain.
© 2020 Published by Elsevier.

Journal Pre-proof
Solubility of 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine in
tetrahydrofuran and alcohols between 288.15 K and 318.15 K
Xianzhao Shao, Maifang Zuo, Changchun Zhao, Wei Wang, and Zhizhou Li
Shaanxi Key Laboratory of Catalysis, School of Chemistry and Environment Science,
Shaanxi University of Technology, Hanzhong 723001, People’s Republic of China
Abstract. 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine (DAPT) was synthesized and
analyzed by nuclear magnetic resonance and Fourier transform infrared spectroscopy,
thermogravimetric and elemental analysis techniques as well as by high-resolution
transmission electron microscopy. DAPT solubility (in tetrahydrofuran, methanol,
ethanol, n-propanol, and isopropanol) in the 288.15-318.15 K range was measured
using the static analytical technique. We also performed quantum chemical
calculations using Gaussian 09 and determined influence of solvent polarity and
solute-solvent interactions on DAPT solubility. Experimental results were treated by
modified Apelblat and Buchowski-Ksiazaczak (λh) equations as well as by the Wilson
and nonrandom two-liquid (NRTL) models. All four models showed excellent
agreement. This study provides valuable data for the purification of DAPT at the
preferential crystallization procedure.
 Corresponding author. Tel.: +86 916 2641660.
Email address: xianzhaoshao@snut.edu.cn (X. Shao).
1

Journal Pre-proof
Keywords. Solubility; 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine; Quantum chemical
calculations; Thermodynamic correlation
2

Journal Pre-proof
1. Introduction
1,3,5-triazine and its derivatives are heterocyclic compounds attracting a lot of
scientific attention because of their biological activity, low toxicity and stability [1-5].
Because of their strong herbicidal and bactericidal properties combined with low
animal toxicity, triazine derivatives are often included into commercial wound-
dressing remedies. Triazine derivatives are also widely used in pharmaceutical
products, such as anti-HIV drugs [2] and antitumor agents [3] because triazine
derivatives act as ligands capable to form complexes of biological significance [6].
Pyridyl-substituted diamino triazines are such compounds capable to form other
multi-dimensional structures through H-bond-based stacking of two amino-groups
and multiple nitrogen atoms [7].
2,4-diamino-6-(4-pyridyl)-1,3,5-triazine (DAPT, C8H8N6, CAS Reg No. 18020-61-
6), containing a pyridyl ring and two amino-groups, is a potential ligand for catalytic
reactions. It is also useful for the fabrication of thin-film molecular devices because
DAPT forms complexes with other compounds [7]. Properties of the products
involving DAPT strongly depend on the purity of the DAPT used. One of the most
well-known and important industrial methods of DAPT separation and purification is
its crystallization from a solution, which is based on compound solubility in a solvent
[8]. DAPT solubility in solvents was not extensively analyzed; yet, like many other
organic compounds, it depends on various parameters such as the rule of “like
dissolves the like”, solvent polarity, intermolecular forces between solute and solvent,
3

Journal Pre-proof
etc [9,10]. Recent developments of theoretical simulations currently allow researchers
to model and analyze compound structures and their properties (including the
influence of intermolecular forces on the compound solubility) using computer
software [11-13].
This paper reports solubility data for DAPT in different solvents (like
tetrahydrofuran, and alcohols like methanol, ethanol, n-propanol, isopropanol)
obtained for the 288.15-318.15 K range and at ambient pressure using gravimetry.
DAPT demonstrated very different solubility in different solvents, which was
determined by quantum chemical calculations. To get a comprehensive picture of the
solubility of DAPT, various models were adapted, which include Apelblat [14] and
the Buchowski-Ksiazaczak (λh) equations [15] as well as the Wilson [16] and
nonrandom two-liquid (NRTL) [17] models.
2. Experimental section
2.1 Materials
All materials were of commercial grades and were used as such. The chemicals,
source, purity and the analytical methods used are summarized in Table 1.
2.2 Apparatus
The measurement of solubility was carried out in an apparatus, the details of which
are described in the literature [18]. The experiments were carried out in a cell fitted
with a jacket and a magnetic stirrer having a particular volume. DCY-3006 thermostat
(manufactured by Shanghai Laboratory Instrument Works) capable of ± 0.05 K
4

Journal Pre-proof
temperature control was used in a circulating water bath. Inner chamber temperature
was measured using a calibrated thermometer with ± 0.05 K accuracy. AR124CN
analytical balance (OHAUS) with ± 0.1 mg precision was also used. Fourier-
transform infrared (FT-IR) spectroscopy was performed using Nicolet 6700
instrument. For this purpose, samples were ground with KBr and then pressed until
1
13
clear pellets were obtained. H NMR and C NMR were performed by Bruker 400
spectrometer. The sample composition was determined using Vario EL Cube
(Elementar, Germany). Thermogravimetric analysis (TGA) was carried by a Mettler
TGA/DSC-1 instrument in the 303.13-823.15 K temperature range at 10 K/min
heating rate under flowing N2 atmosphere. High-resolution transmission electron
microscopy (HRTEM) data was collected by a FEI Tecnai G2 F20 operated at 200 kV.
2.3 Synthesis and Characterization of DAPT
DAPT was synthesized by using a modified literature method [19]. A mixture
containing 1.0411 g of 3-cyanopyridine (10 mmol), 0.8408 g of dicyandiamide (10
mmol), and 0.5 g of KOH (8.9 mmol) dissolved in 50 mL of 2-methoxy-ethanol was
heated for 2 h under refluxing condition. After the solution cooled naturally to
ambient temperature, formed precipitate was filtered. The solid was washed with hot
water after filtration to yield the pure product as a white powder (1.731 g, 9.2 mmol,
92% yield. Scheme 1 gives the detailed synthetic procedure of DAPT. The 1H and 13C
NMR spectra of DAPT are shown in Fig. 1. Anal. Calcd. (%) for C8H8N6: C, 51.06; H,
4.28; N, 44.66. Found (%): C, 50.96; H, 4.31; N, 44.23. 1H NMR (DMSO-d6) ppm, δ:
5

Journal Pre-proof
9.36 (1H, H-3’), 8.70 (1H, H-5’), 8.48 (1H, H-1’), 7.52 (1H, H-6’), 6.89 (4H, NH2).
13C NMR (DMSO-d6) ppm, δ: 169.25 (C-6), 167.74(C-2 and C-4), 152.13(C-3’),
149.43(C-5’), 135.43(C-1’), 132.92(C-2’), 123.90(C-6’) (For numbering, see structure
formula in Scheme 1). FTIR (KBr, cm-1) ν: 3466-3341, 3204, 1644, 1594, 1548, 1453,
1395, 807.
HRTEM helped us to analyze the shapes of the formed crystals and to analyze the
DAPT microstructure. DAPT was found to have small pin-like structures of 5 μm
with thickness varying from mono to few layers.
TGA and DSC were performed in 303.15-823.15 K temperature range at 10 K/min
heating rate under constant N2 flow equal to 50 mL/min (see Figure 3). The moisture
adsorbed on the surface of the sample due to exposure in the ambient atmospheric
condition was the reason behind the initial mass loss of the sample. From 525.15 K to
578.32 K temperature range, the sample was observed to loss 80% of the initial
weight with almost complete decomposition at 823.15 K. Melting point of DAPT was
characterized as 521.48 K with an uncertainty of ± 0.78 K. The fusion enthalpy of
DAPT was 96.50 kJ·mol1 with the relative uncertainty of ± 0.82 kJ·mol1.
2.4 Solubility Measurement
Solubility measurement for DAPT in different solvents including tetrahydrofuran,
methanol, ethanol, n-propanol, and isopropanol were carried out using a static
equilibrium technique. For this purpose, excess DAPT was added in the pure solvent
with stirring of the solution constantly for a minimum of 4 h under a constant
6

Journal Pre-proof
temperature. The stirring was left alone to settle down and obtain a clear solution. The
clear supernatant was transferred into a preliminary-weighed 5.0 mL vial using a
preheated on-off injector coupled with a 0.2 µm PTFE filter, after which the vial was
immediately covered. After measuring the weight of the vial the sample was
evaporated under vacuum drying oven at 353.15 K which is well below the
decomposition temperature of DAPT (464 K) and it was continued till a constant
weight was reached. Each experiment was carried out in triplicate to verify the result.
The mean values of the solubility in a mole fraction were calculated from three
different samples at each temperature. The solubility of DAPT in each solvent was
determined using the equation shown below:
m1 M1
(1),
x 
m1 M1  m2 M2
where, x is the mole fraction of the solute, m1, m2 represent the mass of the solute,
solvent, and M1, M2 are the molecular weight of the solute, solvent, respectively.
2.5 Density Functional Theory Calculations of Interaction Energy
Gaussian 09 method [20] was used to carry out the calculation based on Density
functional theory (DFT) for the identification of interaction profiles of DAPT with
various solvents. It was well known from earlier reports that solubility data could be
well explained by DFT based calculations [11-13]. Frequency analysis and Geometry
optimizations were performed at B3LYP/6-311G (d, p) levels. Zero-point corrections
to energies were included in the frequency analysis along with the thermochemical
information at NTP. Default values in Gaussian were adopted based on the
7

Journal Pre-proof
convergence criteria. The total energies of the isolated DAPT and solvent molecules
were subtracted from the energies of their (1:1) complex to obtain the gas-phase
(solute + solvent) interaction energies. The interaction energy can be defined as [12]:
Einter  (E01  E0  E1)
(2)
where E1 is the total initial energy of DAPT, E0 is initial solvent energy and E0-1 is
the energy of the DAPT-solvent complex.
3. Results and discussion
3.1 Solubility Determination in the Selected Solvents
Table 2 and Figure 4 present DAPT solubility data in various solvents studied at
different temperatures. DAPT solubility in all solvents increased as temperature
increased. Maximum DAPT solubility was in THF. In alcohol, the DAPT solubility
was slowly increased with increasing temperature. The solvents had the following
order for solubility of DAPT: tetrahydrofuran > methanol > ethanol > n-propanol >
isopropanol. In general, solvent polarity plays the most defining factor playing a role
in the material solubility [21,22]. The polarity of the solvents used in this work can be
expressed as following [23]: methanol > ethanol > isopropanol > tetrahydrofuran > n-
propanol. This order does not agree with the DAPT solubility in these solvents. Thus,
in the case of DAPT, solvent polarity was not the dominant factor for its solubility
degree. It is indeed the intermolecular interactions between solvent molecules and
DAPT that determine DAPT solubility. The calculated values of intermolecular
interaction energies, described at the B3LYP/6-311G (d, p) level, are presented in
8

Journal Pre-proof
Table 3. It is evident from Table 3 that THF-DAPT interaction is stronger (22.9
kJ/mol) in comparison to the other solvents. This can be explained on the basis of
interaction of DAPT via NH (from NH2 group) with the oxygen atom of furan ring
can provide a lone pair of electrons to hold together by a strong N–H ∙ ∙ ∙ O bond
(Figure 5). In the case of alcohols, the hydroxyl group formed a weak bond of O–H ∙ ∙
∙ N (pyridine or triazine) type, having interaction energies of 17.4, 16.8, 16.6 and 15.0
kJ/mol for methanol, ethanol, n-propanol and isopropanol, respectively. The larger the
energy value of Einter, the stronger interactions occurred between DAPT and the
solvent molecules. So the THF can dissolve the largest amount of solute. All these
results together suggested that the polarities of the solvents and the energy of
intermolecular interactions could indeed play a key role in affecting the solubility
behavior of DAPT.
3.2 Solubility Correlation
We used modified Apelblat equations to establish how DAPT solubility depends on
temperature [14]:
B
(3)
ln x  A ClnT
T
where, A, B and C are the model parameters of the modified Apelblat equation; x is
a mole of DAPT dissolved and T is the absolute temperature. Table 4 gives the
parameters of the model. The relative and root-mean-square relative deviations (RD
and Rmsrd) for the solvents used in this work were calculated as shown below:
xiexp  xical
RD 
(4)
xiexp
9

Journal Pre-proof


2 1/2
N






1
xiexp  xical

Rmsrd 
(5)
N 
xiexp


i1


xiexp
xical
stand for the
where, N is the total number of experimental data points,
and
values obtained from experiment and calculation, respectively. Table 2 lists the
calculated results, which were then fitted using Equation 3.
The Buchowski-Ksiazaczak λh equation [15] was also used in this work to process
our the solubility data because it describes the solid-liquid equilibria (SLE) very well
[24-26]:


(1 x1)
1
 h( 
T
1
ln 1
)
(6),



x1
Tm

where, Tm is the melting point of the DAPT, and λ and h are model parameters
obtained from the fitting experimental data.
The optimized parameters λ and h for DAPT in five solvents along with the Rmsrd
values are described in Table 5. When the λh equation was used to regress the
experimental data, the average Rmsrd was 2.09% with the maximum being no more
than 7%.
In order to better understand and describe the solubility data, activity coefficient
obtained using Wilson [16] and NRTL [17] models were used to correlate the solid-
liquid equilibria [8, 27-29]:
 H
1
T
m


fus
ln

1
(7)




x
RTm
T
1 1
where, ΔfusH is fusion enthalpy; Tm is melting temperature; R is the gas constant;
and x1 and 1 are mole fraction and activity coefficient of a solute, respectively.
10

Journal Pre-proof
The binary cross-interaction parameters in the Wilson equation (Δλ12 and Δλ21) and
NRTL equation (Δg12 and Δg21) were presumed to be linearly dependent on
temperature:
kij ij  ijT
(8),
where k denotes one of the above-mentioned interaction parameters. In order to fit α
and β obtained from the experiments, the equation was applied:
Np
min f  (ln exp lnical )2
(9)

i
i1
Eqn. 7 was used to calculate the experimental activity coefficients. Now we used
the Levenberg-Marquardt method to minimize Eqn. 9. For each model, the correlation
results were derived by comparison of the root-mean-square relative deviation and the
optimized values of the parameters are shown in Table 4 and the calculated
solubilities with relative deviation are listed in Table 2. Accurate experimental results
could be replicated by the optimized parameters from all the models as evident from
Table 2 and Table 4. When comparing the Rmsrd values among different models, the
modified Apelblat equation, the λh equation, the Wilson and the NRTL models
showed the following values of Rmsrd: 5.67, 10.43, 6.01 and 6.07, respectively.
These values indicate that the modified Apelblat equation provided better-fitting
performance than other models. Thus, it is more accurate to describe processed in the
system studied in this work.
4. Conclusions
11

Journal Pre-proof
DAPT was synthesized and different instrumental techniques like IR, NMR, TGA,
HRTEM were used to characterize the synthesized product. Five different solvents
were used to study the DAPT solubility employing a static analytical technique in the
288.15-318.15 K range. THF showed maximum solubility for DAPT whereas
isopropanol resulting in minimum value. DAPT solubility in the solvents studied in
this work increased as temperature increased. Quantum mechanical calculations
proved that the solubility of DAPT is dependent on the strength of solute-solvent
bonding. The modified Apelblat and λh equations as well as Wilson and NRTL
models were used to assess the validity of our solubility data. The Apelblat equation
described our data more accurately than the λh equation with an average relative error
<0.03. From the obtained results, we can conclude that the solvent dependent
solubility data of DAPT are important in the purification of pyridyldiaminotriazines.
Acknowledgments
This work was supported by the Natural Science Basic Research Program of Shaanxi
(Program No.2018JM2048), Scientific Research Program Funded by Shaanxi
Provincial Education Department (18JK0157), Open Project of Shaanxi Key
Laboratory of Catalysis (SLGPT2019KF01-21), and the Research Fund by Shaanxi
University of Technology (SLGRC14).
References
[1] N.J. Vogelzang, J.E. Herndon, C. Cirrincione, D.C. Harmon, K.H. Antman, J.M.
Corson, Y. Suzuki, M.L. Citron, M.R. Green. Dihydro-5-azacytidine in malignant
mesothelioma: A Phase II trial demonstrating activity accompanied by cardiac
toxicity. Cancer, 79 (1997) 2237-2242.
12

Journal Pre-proof
[2] Z. Brzozowski, F. Saczewski, M. Gdaniec. Synthesis, structural characterization
and antitumor activity of novel 2, 4-diamino-1, 3, 5-triazine derivatives. Eur J. Med.
Chem. 35 (2000) 1053-1064.
[3] C.B. Yoo, P.A. Jones. Epigenetic therapy of cancer: past, present and future. Nat.
Rev. Drug Discov. 5 (2006) 37-50.
[4] K.E. Maly, E. Gagnon, T. Maris, J.D. Wuest. Engineering hydrogen-bonded
molecular crystals built from derivatives of hexaphenylbenzene and related
compounds. J. Am. Chem. Soc. 129 (2007) 4306-4322.
[5] P. Li, H.D. Arman, H. Wang, L. Weng, K. Alfooty, R.F. Angawi, B. Chen.
Solvent dependent structures of melamine: porous or nonporous? Cryst. Growth Des.
15 (2015) 1871-1875.
[6] J.Y. Li, M.J. Xie, J. Jiang, Q.W. Chang, Q.S. Ye, W.P. Liu, J.L. Chen, P. Ning.
Synthesis and crystal structure of two polydimensional molecular architectures from
cobalt (II), copper (II) complexes of 2, 4-diamino-6-pyridyl-1, 3, 5-triazine. Asian J.
Chem. 26 (2014) 419-422.
[7] A. Duong, M.A. Dubois, T. Maris, V. Metivaud, J.H. Yi, A. Nanci, A. Rochefort,
J.D. Wuest. Engineering homologous molecular organization in 2D and 3D.
Cocrystallization of pyridyl-substituted diaminotriazines with alkanecarboxylic acids.
J. Phys. Chem. C 115 (2011) 12908-12919.
[8] J.M. Prausnitz, R.N. Lichtenthaler, E.G. Azevedo. Molecular Thermodynamics of
Fluid-Phase Equilibria, 3rd ed., Prentice Hall, New York, 1999.
[9] W.L. Smith. Selective solubility: “Like Dissolves Like”. J. Chem. Educ. 54 (1977)
228-229.
[10] J.Q. Liu, H. Chen, S.F. An, T.T. Li. Solubility measurement and correlation of 2-
phenyl-1H-indole in fourteen mono organic solvents from 289.05K to 338.55K. J.
Mol. Liq. 302 (2020) 112491.
[11] H. Zhang, Q. Yin, Z. Liu, J. Gong, Y. Bao, M. Zhang, H. Hao, B. Hou, C. Xie.
Measurement and correlation of solubility of dodecanedioic acid in different pure
solvents from T = (288.15 to 323.15) K. J. Chem. Thermodyn. 68 (2014) 270-274.
[12] X. Shao, H. Ge, Z. Li, C. Ren, J. Wang. Solubility of methylphosphonic acid in
selected organic solvents. Fluid Phase Equilib. 390 (2015) 7-13.
[13] C.Yu, Z. Huang, Z. Zeng, W. Xue. Thermodynamic models for correlation of
solubility of hexaquocobalt(II) bis(p-toluenesulfonate) in liquid mixtures of water and
ethanol from 288.15 to 333.15 K. J. Solution Chem. 45 (2016) 395-409.
[14] Apelblat, A.; Manzurola, E. Solubilities of o-acetylsalicylic, 4-aminosalicylic, 3,
5-dinitrosalicylic, and p-toluic acid, and magnesium-DL-aspartate in water
fromT=(278 to 348) K. J. Chem. Thermodyn. 31 (1999) 85-91.
[15] H. Buchowski, A. Ksiazczak, S. Pietrzyk. Solvent activity along a saturation line
and solubility of hydrogen-bonding solids. J. Phys. Chem. 84 (1980) 975-979.
[16] G.M. Wilson. Vapor-liquid equilibrium. XI. A new expression for the excess free
energy of mixing. J. Am. Chem. Soc. 86 (1964) 127-130.
13

Journal Pre-proof
[17] H. Renon, J.M. Prausnitz. Local compositions in thermodynamic excess
functions for liquid mixtures. AIChE J. 14 (1968) 135-144.
[18] M.Y. Li, D. Constantinescu, L.S. Wang, A. Mohs, J. Gmehling. Solubilities of
NaCl, KCl, LiCl, and LiBr in methanol, ethanol, acetone, and mixed solvents and
correlation using the LIQUAC model. Ind. Eng. Chem. Res. 49 (2010) 4981-4988.
[19] A. Diaz-Ortiz, J. Elguero, C. Foces-Foces, A. de la Hoz, A. Moreno, M. del
Carmen Mateo, A. Sanchez-Migallon, G. Valiente. Green synthesis and self-
association of 2, 4-diamino-1, 3, 5-triazine derivatives. New J. Chem. 28 (2004) 952-
958.
[20] M.J. Frisch, G.W. Trucks, H.B. Schlegel, et al. Gaussian 09, revision A.01;
Gaussian, Inc., Wallingford CT, 2009.
[21] S. Imran, A. Hossain, K.Mahali, P.S. Guin, A. Datta, S. Roya. Solubility and
peculiar thermodynamical behaviour of 2-aminobenzoic acid in aqueous binary
solvent mixtures at 288.15 to 308.15 K. J. Mol. Liq. 302 (2020) 112566.
[22] K. Mahali, P.S. Guin, S. Roy, B.K. Dolui.Solubility and solute–solvent
interaction phenomenon of succinic acid in aqueous ethanol mixtures. J. Mol. Liq.
229 (2017) 172–177.
[23] B.E. Poling, J.M. Prausnitz, J.P. O’Connell, The Properties of Gases and Liquids,
5th ed., McGrawHill, New York, 2001.
[24] X. Ma, Q. Zhao, Q. Liu, Y. Xing, R. Fan, R. Tian. Synthesis and solubility of
5,5-dimethyl-2-(phenyl(phenylamino)methyl)-1,3,2-dioxaphosphinane 2-oxide in
selected solvents between 278.15 K and 347.15 K. J. Chem. Eng. Data 62 (2017)
4196-4204.
[25] Y. Wang, Y. Chen, P. Zhu, Y. Bao, C. Xie, J. Gong, X. Jiang, B. Hou, W. Chen.
Measurement and correlation of the solubility of 2,6-dihydroxybenzoic acid in
alcohols and binary solvents. J. Chem. Eng. Data 62 (2017) 3009-3014.
[26] K.H. Kim, H.K. Oh, B. Heo, N.A. Kim, D.G. Lim, S.H. Jeong. Solubility
evaluation and thermodynamic modeling of β-lapachone in water and ten organic
solvents at different temperatures. Fluid Phase Equilib. 472 (2018) 1-8.
[27] Y.J. Li, K. Wu, Y. Li, Y. Zhang, J.J. Liu, X.Z. Wang. Solubility in different
solvents, crystal polymorph and morphology, and optimization of crystallization
process of AIBN. J. Chem. Eng. Data 63 (2018) 27-38.
[28] P. Zhang, R. Zhao, C. Zhang, T. Lia, B. Ren. Solubility determination and
correlation of cyromazine in sixteen pure solvents and mixing properties of solutions.
Fluid Phase Equilib. 475 (2018) 77-88.
[29] H. Shekaari, M.T. Zafarani-Moattar, M. Mokhtarpour. Experimental
determination and correlation of acetaminophen solubility in aqueous solutions of
choline chloride based deep eutectic solvents at various temperatures. Fluid Phase
Equilib. 462 (2018) 100-110.
14

Journal Pre-proof
Table 1. Purity of the chemicals used in the study
Chemical name
Source
Purity (mass
fraction)
≥0.993
≥0.99
Analysis
method
HPLCa
HPLC
HPLC
GCb
DAPT
Synthesized in this work
Dicyandiamide
3-Cyanopyridine
Shanghai Aladdin Chemical Reagent Co.
Shanghai Aladdin Chemical Reagent Co.
≥0.98
2-Methoxyethanol Shanghai Aladdin Chemical Reagent Co.
≥0.98
Tetrahydrofuran
Methanol
Shanghai Aladdin Chemical Reagent Co.
Shanghai Aladdin Chemical Reagent Co.
Shanghai Aladdin Chemical Reagent Co.
Shanghai Aladdin Chemical Reagent Co.
Shanghai Aladdin Chemical Reagent Co.
≥0.995
≥0.995
≥0.995
≥0.995
≥0.995
GC
GC
Ethanol
GC
n-Propanol
IsoPropanol
GC
GC
aHigh-performance liquid chromatography. bGas-liquid chromatography.
15

Journal Pre-proof
Table 2. Experimental and theoretically predicated (using the methods listed below) mole fraction
solubility (x) of DAPT in different solvents at 0.1 MPa.a
T/K
102x
Apelblat equation
λh equation
NRTL
Wilson
102RD
102xc
102RD 102xc 102RD 102xc
102RD 102xc
Tetrahydrofuran
288.15 0.3081
293.15 0.3339
298.15 0.3622
303.15 0.3897
308.15 0.4071
313.15 0.4329
318.15 0.4552
Methanol
0.3073
0.3342
0.3605
0.3857
0.4098
0.4323
0.4530
-0.26
0.09
0.3110
0.3352
0.3596
0.3841
0.4087
0.4331
0.4574
0.96
0.39
-0.72
-1.43
0.39
0.05
0.48
0.3121 1.29
0.3348 0.28
0.3584 -1.06
0.3827 -1.80
0.4078 0.16
0.4336 0.15
0.4601 1.07
0.3122
0.3349
0.3584
0.3827
0.4078
0.4337
0.4603
1.34
0.31
-1.04
-1.79
0.18
0.18
1.12
-0.48
-1.02
0.65
-0.15
-0.48
288.15 0.1377
293.15 0.1494
298.15 0.1698
303.15 0.1977
308.15 0.2143
313.15 0.2369
318.15 0.2687
Ethanol
0.1360
0.1527
0.1713
0.1919
0.2147
0.2399
0.2677
-1.25
2.23
0.90
-2.92
0.19
1.26
-0.39
0.1337
0.1523
0.1724
0.1938
0.2165
0.2404
0.2653
-2.91
1.96
1.52
-1.97
1.02
1.46
-1.28
0.1364 -0.93
0.1528 2.26
0.1711 0.77
0.1916 -3.08
0.2146 0.12
0.2401 1.35
0.2684 -0.11
0.1360
0.1529
0.1715
0.1921
0.2149
0.2400
0.2677
-1.21
2.34
1.02
-2.82
0.28
1.32
-0.37
288.15 0.07339 0.07288 -0.69
293.15 0.08134 0.08271 1.68
298.15 0.09246 0.09401 1.68
0.07075 -3.60
0.08203 0.85
0.09452 2.22
0.07276 -0.86
0.08249 1.41
0.09377 1.42
0.1068 -2.63
0.1218 0.02
0.1390 1.34
0.1587 -0.37
0.07270 -0.93
0.08257 1.51
0.09388 1.54
303.15 0.1097
308.15 0.1218
313.15 0.1372
318.15 0.1593
n-Propanol
0.1070
0.1220
0.1393
0.1591
-2.43
0.18
1.52
-0.10
0.1082
0.1232
0.1394
0.1568
-1.34
1.13
1.60
-1.54
0.1069
0.1218
0.1390
0.1588
-2.59
0.01
1.31
-0.33
288.15 0.06406 0.06387 -0.30
0.05992 -6.47
0.06418 0.18
0.06397 -0.14
16

Journal Pre-proof
293.15 0.07201 0.07197 -0.05
298.15 0.08302 0.08202 -1.21
303.15 0.09417 0.09444 0.29
0.07103 -1.36
0.08358 0.67
0.09763 3.68
0.07216 0.21
0.07237 0.51
0.08247 -0.66
0.09477 0.64
0.08225 -0.93
0.09484 0.71
0.1104 -0.21
0.1295 0.74
0.1527 -0.43
308.15 0.1106
313.15 0.1285
318.15 0.1534
Isopropanol
0.1098
0.1288
0.1524
-0.72
0.24
0.1132
0.1304
0.1492
2.38
1.50
-2.74
0.1100
0.1290
0.1533
-0.57
0.40
-0.67
-0.10
288.15 0.04258 0.04225 -0.77
293.15 0.05056 0.05165 2.16
298.15 0.06412 0.06315 -1.51
303.15 0.07871 0.07723 -1.88
308.15 0.09251 0.09445 2.09
0.04024 -5.49
0.05081 0.50
0.06350 -0.97
0.07853 -0.23
0.09612 3.90
0.04239 -0.45
0.05178 2.42
0.06334 -1.22
0.07752 -1.52
0.09485 2.53
0.1160 0.24
0.1417 -0.10
0.04213 -1.07
0.05187 2.59
0.06350 -0.97
0.07741 -1.66
0.09420 1.83
313.15 0.1157
318.15 0.1418
0.1155
0.1412
-0.18
-0.43
0.1164
0.1396
0.63
0.1150
0.1419
-0.63
0.04
-1.55
aStandard uncertainties u are u(T) = ±0.05 K, ur(p) = 0.05, ur(x) = 0.03.
17

Journal Pre-proof
Table 3. Calculated interaction energy between DAPT and solvents
Interaction energy (kJ·mol1)
solvents
Tetrahydrofuran
Methanol
22.9
17.4
16.8
16.6
15.0
Ethanol
n-Propanol
Isopropanol
18

Journal Pre-proof
Table 4. DAPT parameters and Rmsrd obtained by applying modified Apelblat and λh equations
for the solvents
Apelblat equation
λh Equation
solvent
A
B
C
Rmsrd/%
λ
h
Rmsrd/%
Tetrahydrofuran 128.25
-7042.7 -19.351 0.54
-58.409 -589.66 8.7865 1.59
6.2133
7.5222
4.6595
7.1562
25.144
279.03
334.48
570.87
425.65
163.87
0.76
1.83
1.95
3.23
2.66
10.43
Methanol
Ethanol
-138.71 3914.1
-355.33 13445
20.818
53.203
24.431
1.43
0.62
1.49
5.67
n-Propanol
Isopropanol
Overall
-159
3707.4
19

Journal Pre-proof
Table 5. Regression parameters and Rmsrd for DAPT obtained using Wilson and NRTL models for the solvents
Wilson
NRTL
Solvent
α12
β12
α21
-61436
-86627
-84783
-87137
-67415
β21
179.78
188.91
185.11
202.91
135.92
Rmsrd%
1.04
α12
-86599
-65809
-63760
-34328
-45916
β12
188.47
139.59
131.1
α21
-99.251
-10554
-16114
-16813
-13921
β21
27.796
31.452
56.322
42.412
40.892
Rmsrd%
1.02
16.294
1.0503
THF
Methanol
80.829
9566.6
13.736
-17.253
-77.548
-323.45
1.61
1.61
Ethanol
1.42
1.41
n-Propanol 26839
Isopropanol 111320
overall
0.48
58.649
83.761
0.56
1.46
1.49
6.01
6.07
20

Journal Pre-proof
Scheme 1. Synthetic route of DAPT.
21

Journal Pre-proof
13C NMR
1H NMR
H2O
DMSO-d6
12
10
8
6
4
2
0
200
180
160
140
120
100
80
60
40
20
0
ppm
ppm
Figure 1. 1H NMR and 13C NMR spectra of DAPT.
22

Journal Pre-proof
Figure 2. HRTEM micrographs of DAPT.
23

Journal Pre-proof
Figure 3. TGA/DSC curves for DAPT recorded under N2 flow at 10 K/min heating
rate.
24

Journal Pre-proof
Figure 4. Experimental solubility of DAPT in different solvents: , tetrahydrofuran;
, methanol; , ethanol; , n-propanol; , isopropanol.
25

Journal Pre-proof
b
a
c
d
e
Figure 5. Interactions between DAPT and tetrahydrofuran (a), methanol (b), ethanol
(c), n-propanol (d), and isopropanol (e).
26

Journal Pre-proof
Graphical Abstract
Interactions between DAPT and different solvents
27

Journal Pre-proof
Author Statement
Conceptualization, X. Shao, and Z. Li; Investigation, X. Shao, M. Zuo, and C. Zhao;
Writing – Original Draft, X. Shao, and W. Wang; Review & Editing, X. Shao, and W.
Wang; Funding Acquisition, X. Shao, and Z. Li.
28

Journal Pre-proof
Declaration of interests
☒ 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.
☐The authors declare the following financial interests/personal relationships which
may be considered as potential competing interests:


29