Structure-Physical Properties Relationship of Eutectic Solvents Prepared from Benzyltriethylammonium Chloride and Carboxylic Acids

Deep eutectic solvents (DESs) have attracted the attention of the researchers as alternative solvents due to desirable properties such as easy preparation and high thermal stability. In this work, it was reported the preparation of five DESs from benzyltriethylammonium chloride (BTEAC) as quaternary ammonium salt (QAS) and carboxylic acids (oxalic, malonic or benzoic) as hydrogen bonding donor (HBD), which four were not reported so far. Furthermore, it was presented the first type III liquid DES at room temperature from benzoic acid and shown by interaction energy calculations why the formation of benzyltriethylammonium chloride:benzoic acid (BTEAC:BA) is favored over choline chloride:benzoic acid (ChCl:BA). The optimized geometries showed the Cl···π interaction is determining for decreasing the freezing point of benzyltriethylammonium chloride:benzoic acid mixture. Infrared spectra showed evidence for the existence of hydrogen bonds in DESs. Physical (freezing point, density and refractive index), thermal (thermogravimetric analysis) and rheological characterizations were performed for all solvents. The structure of HBDs affected the results on all evaluated properties and proved that it could be tunable. The prepared DESs were stable thermically and can be used in a wide range of temperature. Finally, rheological studies showed that Newtonian or non-Newtonian behavior can be observed by the nature of HBD.


Structure-Physical Properties Relationship of Eutectic Solvents Prepared from Benzyltriethylammonium Chloride and Carboxylic Acids
Guilherme C. Paveglio, * ,a Fernanda A. S. C. Milani, b André C. Sauer, c Daiane Roman, a Alexandre R. Meyer d and Lucas Pizzuti * ,a (ChCl) due to physical (highly soluble in water), chemical (formation of DESs with various types of hydrogen bonding donors (HBDs)) and economical (low price and high availability) aspects. 2 Carboxylic acids have been widely used as HBDs in the preparation of type III DESs with specific properties. [8][9][10][11] In 2014, Florindo et al. 8 prepared DESs from ChCl and carboxylic acids (levulinic, glutaric, malonic, oxalic, and glycolic) to evaluate the influence of HBDs in the thermophysical properties. Density, viscosity, and refractive index were affected by the nature of the HBD and proved that molar ratio variation or structural changes in HBD allowed the preparation of a range of DESs with tunable properties. 8 Moreover, DESs prepared from malonic, anhydrous or hydrated oxalic acid as HBD and choline chloride as QAS has been applied in the pretreatment, extraction, catalysis of biomass and food waste and the results show environmental and economic benefits. 1 In this context, the preparation of new type III DESs from carboxylic acids and quaternary ammonium salts can contribute to improving the results in the mentioned areas. Benzyltriethylammonium chloride (BTEAC) is a cationic surfactant and have been applied in electrochemistry, photochemistry, agent decontaminant and as a phase-transfer catalyst in organic synthesis. [12][13][14][15][16][17] Although BTEAC is used for several applications, it as QAS was under-explored to date in the preparation of type III DESs. In 2017, Taysun et al. 18 tested the effect of HBDs with one, two or three acidic groups (p-toluenesulfonic monohydrate, oxalic dihydrate, and citric monohydrate acids) on the density, refractive index, viscosity, conductivity, and pH of eutectic solvents prepared from BTEAC. The authors 18 pointed out that BTEAC:citric acid monohydrate (1:1) provided a very high viscosity, which hampered the handling and the determination of density and viscosity. Recently, DESs have been used successfully as a solvent in the synthesis of 1,2,4-triazolo[1,5-a]pyrimidines and 4-acyl-1-substituted-1,2,3-triazoles. 19,20 In the continuation of our studies, the limited number of DESs prepared from BTEAC and HBDs associated with the importance of designing new solvents with tunable properties motivated us to evaluate these systems. In this work, it was chosen only mono and dicarboxylic acids (benzoic (BA), malonic (MA), and oxalic acid (OA)) as HBDs and proposed the preparation and physical (freezing point, density and refractive index), thermal (thermogravimetric analysis), and rheological characterization of DESs from these acids and BTEAC as QAS. Five DESs were prepared, which four were not reported so far. Our goal was to study the impact of the structure of HBDs on the physical properties of DESs. Furthermore, infrared (IR) spectroscopy was used to compare the spectra of DESs with their individual components. Finally, quantum chemical calculations were performed to generate insights about the interactions in the formation of liquid deep eutectic solvents with benzoic acid.

Materials
All reagents were purchased from Sigma-Aldrich (Milwaukee, USA) with a stated purity of 99%. All chemicals were dried under vacuum for 48 h and used in the preparation of DESs as supplied without further purification. All details about the chemicals used in this work are given in Table 1.
Preparation of DESs BTEAC (11.388 g, 50 mmol) and acid (1:1 or 1:2 molar ratio) were added into a round bottom flask. The mixture was heated at 100 °C and stirred for 15 min for malonic acid and 1 h for oxalic and benzoic acids. 8,10 Figure S1 (Supplementary Information (SI) section) shows the acronyms, molar ratios, and apparency of DESs prepared in this work.

Methods
Quantum chemical calculations were performed with the ORCA 4.2.0 program package. 21,22 The structures

Preparation of DESs
Initially, four eutectic solvents were prepared from BTEAC and oxalic acid dihydrate, oxalic acid, malonic acid and benzoic acid at a 1:1 molar ratio to evaluate the effect of HBDs structure on physical properties. Afterward, a DES was prepared from BTEAC and malonic acid at a 1:2 molar ratio to compare its physical properties to the 1:1 mixture (Table 2).

Spectroscopic data
Nuclear magnetic resonance ( 1 H, 13 C, and 35 Cl nucleus) and infrared spectroscopies were performed for all DESs (Figures S3-S23, SI section). Table 3 shows the characteristic infrared stretches of DESs and their HBDs. Table 4 shows the values determined for DESs freezing points (fp DES ) and calculated for the difference between the QAS freezing point (fp QAS , °C) and DES freezing point (fp DES , °C), which were called Δfp. The formula used to calculate Δfp was:

Quantum chemical calculations
Quantum mechanical calculations were performed to provide energy data at the ωB97X-D3/cc-pVDZ level of theory, aiming insights about the interaction between HBD and QAS in the formation of DESs. Due to its good performance in many applications, the ωB97X-D3 method was chosen, including the analysis of bonded and nonbonded interactions. 23,24 The cc-pVDZ basis set was used by its good relationship between computational cost and accurate results. The optimized geometries ( Figure S2), the atomic coordinates for ChCl:BA (Table S1), and BTEAC:BA (Table S2) and the DESs intermolecular interactions energies (Table S3) are shown in the SI section.

Thermogravimetric analysis
The temperature at which there was a loss of 10% of the mass of the compound (T onset (10%) ), the maximum of the derivative thermogravimetry (DTG) curve (T d ), and the final decomposition temperature (T f ) obtained for DESs are shown in Table 5. The thermograms of BTEAC, HBDs, and DESs are shown in Figures S24-S32 in the SI section. Table 6 presents the density of pure HBDs (ρ HBD) given by the supplier, as well as the density of DESs (ρ DES) and the molar mass (MM DES) determined in this work. According to the literature, 25 DESs are mixtures, and the average molar mass (MM) is calculated using the following formula: x 1 MM 1 + x 2 MM 2 , where x is the molar fraction and MM is the molar mass of each component.   Rheological behavior Figure 1 shows the viscosity (Pa s) as a function of shear rate (s −1 ) at 25 °C for all DESs prepared. Tables S4-S7  (SI section) show the values of shear rate, shear stress, viscosity, and torque obtained for all DESs. Table S8 (SI  section) shows the values of temperature, shear stress, viscosity, and torque obtained for BTEAC:BA (1:1).   (756 and 713). IR spectra of all DESs did not show differences in the vibrational wavenumbers attributed to BTEAC compared to the pure BTEAC spectrum, as illustrated by the BTEAC and BTEAC:BA (1:1) overlapped spectra ( Figure S18, SI section). This indicates that the cationic fragment of BTEAC does not interact with HBDs when DESs are formed. Such information evidence that shifts are associated with hydrogen bonding between the anion (Cl − ) and HBD. Figures S19-S23 (SI section) show the overlapping of DESs and their HBDs infrared spectra. DESs prepared from oxalic acid anhydrous, oxalic acid dihydrate,     Liquid DESs at room temperature prepared from oxalic acid (ChCl:OA 1:1; tetrabutylammonium bromide (TBAB):OA 1:1) and malonic acid (ChCl:MA 1:1 and 1:2; TBAB:MA 1:1) are well known. 8,10,11 On the other hand, to the best of our knowledge, type III liquid DESs at room temperature were not prepared from benzoic acid. For example, the mixtures ChCl:BA (1:1) and trimethylglycine:BA (1:2) presented freezing points of 95 and 53 °C, respectively. 9,10 Thus, BTEAC:BA (1:1) is the first type III liquid DES at room temperature prepared from benzoic acid. Benzoic acid is used as food preservatives due to the inhibition of fungi, yeasts, and some bacteria. 31 Moreover, benzoic acid and their derivates are used in medicine and cosmetic formulations. [32][33][34] Due to these applications, the design of new eutectic solvents from benzoic acid is a significant contribution to the area. This result led us to the first question: why is BTEAC:BA (1:1) liquid at room temperature? The first work on type III eutectic solvents reported by Abbott et al. 29 showed two key patterns concerning the cationic fragment of the QAS: (i) as cation symmetry decreases, the freezing point of the DES decreases; (ii) the presence of groups capable of performing stronger intermolecular interactions (hydrogen bond or dipole-dipole) with HBD favored the reduction of freezing point compared to groups performing London or π-π interactions. In the case of BTEAC:BA (1:1), the non-symmetry of QAS could lead to the formation of liquid DES with benzoic acid. However, the second trend does not favor our result, since BTEAC does not have polar groups. The second trend observed by Abbott et al. 29 led to a second question: if polar groups often favor the reduction of freezing points, why do other salts such as ChCl not form liquid mixtures with benzoic acid? More recent works 35,36 have attempted to explain the formation of eutectic solvents by theoretical calculations for intermolecular interactions. Therefore, our first goal was to study why liquid DES with benzoic acid was formed only when BTEAC was used. The pharmacological importance of benzoic acid and the fact that BTEAC:BA (1:1) is the first liquid DES at room temperature prepared from benzoic acid motivated us to investigate why the formation of BTEAC:BA (1:1) is favored to ChCl:BA (1:1). Thus, quantum mechanical calculations were performed to provide energy data at the ωB97X-D3/cc-pVDZ level of theory to achieve insights about the interaction between HBD and QAS in the formation of DES. The DESs optimized geometries ( Figure S2, SI section) showed that in both cases, BA interacts preferably with the chloride ion of the QAS. In ChCl:BA, the Cl···HO interaction (distances of 2.119 Å for Cl···H and 3.045 Å for Cl···O) is preferred, whereas the Cl···π interaction (a distance of 3.493 Å between Cl and the ortho carbon of phenyl) is favored in BTEAC:BA.

Refractive index
The freezing point of a substance is directly correlated with the strength of the intermolecular interactions present in its structure. 37 Thereby, the lower the intermolecular interaction strength lower will be its freezing point. The calculated intermolecular interaction energies (Table S3, SI section) showed that the total interaction energy (ΔE INT ) is lower for BTEAC:BA (−122.72 kcal mol −1 ) than for the ChCl:BA (−140.54 kcal mol −1 ) and therefore a lower freezing point is expected for the first one. This finding is corroborated by the data obtained for the E BA···QAS energy (Table S3), which showed that BA interacts more strongly with the BTEAC chloride ion (−29.90 kcal mol −1 ) than the ChCl one (−24.35 kcal mol −1 ). This weakens the coulombic attraction between cation and anion within BTEAC, decreasing the total intermolecular interaction energy and freezing point.
Applicability of solvents depends on the range of temperatures they remain liquids. Determination of freezing point (fp) and thermogravimetric analysis (TGA) give the temperature the DESs solidificate and evaporate or decompose, respectively. The freezing point can be determined by cooling DESs in an ice bath or similar procedures. 18,38 Based on the results shown in Table 4, the standard deviation ranged from 0.5-0.7 °C, which shows that the procedure was accurate. Also, trends were observed in our results compared to data published by Abbott et al. 29 for DESs prepared from ChCl ( Table 4). The freezing points of BTEAC and ChCl are 190 and 302 °C, respectively. Comparison between the values of Δfp in entries 2 and 3 (181 and 268 °C) or 4 and 5 (180 and 292 °C) shows that the interaction between ChCl and oxalic or malonic acid decreases the freezing points more sharply than the interaction between BTEAC and the same HBDs. The difference between the values of Δfp from entries 2 and 3 in Table 4 is 87 °C whereas the difference between Δfp from entries 4 and 5 in Table 4 is 112 °C. However, Δfp is similar for BTEAC:BA (179 °C, entry 6, Table 4) and ChCl:BA (207 °C, entry 7, Table 4). In this case, the difference between the Δfp is only 28 °C.
The thermogravimetric analysis allows determining the maximum of the DTG curve (T d ), final decomposition temperature (T f ), and 10% weight loss (T onset (10%) ) of a sample. These data are important for new DESs characterization and determine the applicability. As expected, the values of T onset (10%) , T d , and T f obtained for our DESs are different from those obtained for both BTEAC and HBDs ( Table 5) (212, 209, 202, and 197 °C, respectively). In addition, BTEAC:MA (1:2) presented two decomposition steps (136 and 196 °C), which are different from neat BTEAC or malonic acid. T onset and T d confirm that DESs thermal behavior is unique and differs from its components. All our DESs completely decompose between 190 and 235 °C, according to the T f values shown in Table 5. The association of freezing point and TGA data allows to say that all eutectic solvents of this work can be used at temperatures between 11 and 125 °C without solidification or decomposition.
Density and viscosity are important to determine the flow behavior of a solvent. 18 Density is an important property in simple procedures such as small scale extractions but also in more complicated applications such as the design for technical applications of new chemical adsorbents. 39 The value of the density (d) is determined by mass (m) to volume (V) ratio: d = m / V. Essentially, the density can be affected by four main factors: temperature, pressure, intermolecular interactions and molar mass. 40 Concerning density, three main trends have been observed in DESs prepared from BTEAC: (i) HBD structure directly affects density; (ii) DESs prepared from HBDs containing two carboxylic acid functions present higher densities; (iii) density increases when the HBD molar ratio increases. The densities of DESs in the 1:1 molar ratio showed the order BTEAC:OA > BTEAC:OA•2H 2 O > BTEAC:MA > BTEAC:BA which coincided with the density order of the respective pure HBDs (OA > OA•2H 2 O > MA > BA) (entries 1-4, Table 6), confirming the first trend. Intermolecular interactions strongly influenced the densities in accordance with trend two. Oxalic acid only performs hydrogen bond interactions, therefore, BTEAC:OA presented the highest density value (1.1854, entry 1, Table 6). Using oxalic acid dihydrate as HBD decreased the density (1.1729, entry 2, Table 6). This effect has already been reported in the literature 8 for other DESs. A spacer group (−CH 2 ) between the carbonyls significantly decreased the density value, as observed for BTEAC:MA (1.1154, entry 3, Table 6). Probably, the addition of this spacer group alters the supramolecular arrangement of the eutectic solvent allowing London interactions (weaker than hydrogen bonds). These weaker interactions leave the molecules more dispersed and decrease the density. The value obtained for BTEAC:BA (1:1) was the lowest one (1.0933, entry 4, Table 6) because benzoic acid presents only one carboxyl group to make hydrogen bonds whereas malonic and oxalic acids present two carboxyl groups. The third trend was followed by the DESs obtained from malonic acid in 1:1 and 1:2 molar ratios (1.1154 and 1.1762, entries 3 and 5, Table 6). A higher density was measured for BTEAC:MA (1:2) due to the increased number of hydrogen bonds which improve the molecular cohesion. The standard deviation values for density ranged from 0.0009-0.0016 g cm −3 . These results indicate that our measurements were accurate and are in accordance with the values already determined for DESs in the literature. 8,18,26,38,41 Viscosity measurements as a function of shear rate determine whether the substance presented Newtonian or non-Newtonian behavior. Newtonian fluids show constant viscosity behavior over the change in shear or external force. On the other hand, non-Newtonian change viscosity as a function of the shear rate. 42 Non-Newtonian fluids are subdivided in dilatant or pseudoplastic. The difference between dilatant and pseudoplastic fluids is that the viscosity of the first increases while the viscosity of the second decreases when the shear rate increases. In this sense, Newtonian fluids can be associated with polymers to improve flow behavior. 43 On the other hand, non-Newtonian fluids can be applied in lubricants, printing technology, damping and braking devices, personal protective equipment, mechanical processing. 44,45 In the case of pseudoplastic fluids, it can be used in water-based paints, medical injection or energy transport fields. 46,47 Knowing DESs rheological properties is important to define their applications. However, our literature search found only three works 48-50 that discuss viscosity as a function of shear rate for DESs containing carboxylic acids as HBDs combined with ChCl and benzyltripropylammonium chloride (BTPAC). Accordingly, this is the first work that discusses the rheological behavior for DESs obtained from BTEAC and carboxylic acids (OA, MA and BA). The nature of the HBD strongly influenced the results since both behaviors (Newtonian and non-Newtonian) were observed for our DESs prepared from BTEAC and carboxylic acids. BTEAC:BA showed a pseudoplastic non-Newtonian behavior (Figure 1a). In contrast, the DESs containing oxalic or malonic acids as HBD exhibited Newtonian behavior (Figure 1b Refractive index is a specific property which can be used to determine the purity of substances. 18 The parameters that affect the refractive index are: temperature (T), concentration, chemical nature, and incident light wavelength (λ). 40 The refractive indexes of DESs in the 1:1 molar ratio showed the order BTEAC:BA > BTEAC:MA > BTEAC:OA > BTEAC:OA•2H 2 O ( Table 7). The refractive index values (1.509-1.559) were significantly affected by the chemical structure of HBDs. DES prepared from oxalic acid dihydrate presented a lower refractive index than anhydrous form (1.50992 and 1.52088, entries 1 and 2, Table 7, respectively). In contrast, BTEAC:BA (1:1) presented higher refractive index value (1.55977, entries 3, Table 7) due to the aromatic ring of benzoic acid being polarizable. 25 BTEAC:MA in 1:1 molar ratio showed higher value (1.53210, entry 4, Table 7) compared to oxalic acid, however, lower than BTEAC:BA (1:1). Moreover, the refractive index decreased (1.53210 to 1.50904, entries 4 and 5, Table 7) when the molar ratio of HBD (malonic acid) was changed from 1:1 to 1:2 for BTEAC:MA. Regarding the standard deviation calculated for the refractive index, the values ranged from 0.00055-0.00152, which are in accordance with works reported in the literature. 18,51 The results of Table S9 (SI section) show that the refractive index values decreased at higher temperatures for all eutectic solvents. The increase in temperature causes thermal expansion and allows light rays to pass through the medium. 18,52 The literature 8,26 shows type III DESs prepared from carboxylic acids exhibited the same behavior.

Conclusions
It was reported herein the preparation of four new deep eutectic solvents from BTEAC and organic acids and evaluated the effect of HBD on structural, physical, and rheological properties. FTIR experiments showed frequency shifts for the C=O, C−O and O−H vibrations, in comparison to the pure BTEAC and HBDs FTIR spectra, which evidenced the hydrogen bonds formation in all eutectic solvents. Quantum chemical calculations gave insights to explain why BTEAC favored the formation of liquid DES at room temperature with benzoic acid, and the result corroborated with freezing point. The determination of freezing points and onset temperatures showed DESs prepared were stable thermically until 126 °C and can be used in a liquid state over a wide temperature range. The flow behavior study showed that the choice of HBD is a key factor for adjusting both density and viscosity of DESs. The refractive index was influenced by temperature, molar ratio, and structure of HBD. All these data help to understand the structural effects of HBDs on the physical properties of DESs and assist in the preparation of DES with tunable properties.