Comparison of Tautomerization, Vibrational Spectra and UV-Vis Analysis of β -Ketoester With Acetylacetone. An Experimental and Theoretical Study

In this study, the equilibrium constants, keto-enol ratio, and hydrogen bond strength among keto and cis-enol forms of acetylacetone (AA), methyl acetoacetate (MAA), ethyl acetoacetate (EAA), ethyl 2-methyl acetoacetate (EMA), benzyl acetoacetate (BAA), and ethyl benzoyl acetone (EBA) have been investigated using density functional theory (DFT), compared with the experimental results. According to the obtained results, the relative energy of cis-enol and keto forms of  -ketoesters in gas phases is greater than that of acetylacetone, so the enol form of acetylacetone is more stable and it causes to increase its strength of intramolecular hydrogen bond. The electronic properties of these compounds were surveyed by NMR, FT-IR, and UV-Vis spectra. Besides, the obtained outcomes showed that the keto forms of  -ketoesters in the presence of acetonitrile and carbon tetrachloride as a solvent have a high absorption coefficient due to the polarity of the solvent.


Introduction
-Dicarbonyl compounds included -diketones and -ketoesters have various keto and enol forms. The phenomenon of keto-enol equilibrium is called "Tautomerism" and the forms are known as tautomers. The keto-enol equilibrium depends on the electric features of the substituents, temperature, and the environment of the solvent. Under usual conditions when one tautomer is more stable than the others, it is known as the "stable form". An intramolecular hydrogen bond is present in closed cis-enol forms of -dicarbonyl and it leads to a stable form of the tautomer [1][2].
In the structure of -ketoesters, the presence of the alkoxy group decreases the enol content and results in the reduction of intramolecular hydrogen bond strength [3][4][5][6]. Furthermore, the intramolecular hydrogen bond (IHB) in -ketoesters is weaker than the -diketones.
According to theoretical and experimental data from several literature, the electron-donating and electron-withdrawing groups which are present in the and -position of -dicarbonyl, influence the intramolecular hydrogen bond strength [7][8][9]. Bunkoeda et.al established the transparent sol-gels with captured sensitive and selective substances for the detection of formaldehyde [10]. They investigated the sensitivity of the reactions of acetylacetone and methyl acetoacetate with formaldehyde. The results showed that acetylacetone reacted faster with formaldehyde than methyl acetoacetate. Fokendt et.al, using 1 H NMR spectroscopy, investigated the intermolecular tautomeric interaction of keto-enol -dicarbonyl compounds [11]. They found that the proton chemical shift of enol form in acetylacetone (AA), methyl acetoacetate (MAA) and, ethyl acetoacetate (EAA) in the pure liquid phase, is 14.6, 11.96, 11.6 ppm, and in the gas phase, is 15.2, 11.97, 12.01 ppm, respectively. According to the above studies, a definite explanation of the chemical reactivity is not easy without having qualitative and quantitative information about tautomers [12].
The present study aims to investigate the hydrogen bond strength and thermodynamic and geometry parameters of some -ketoesters such as "MAA, EAA, EMA" and comparing them with AA, benzylacetoacetate (BAA), and ethyl benzoylacetate (EBA) in the gas and solution phase. All theoretical results such as density functional theory (DFT), atoms-in-molecules (AIM), and natural bond orbital (NBO), compared with experimental methods included 1 H-NMR, FT-IR, and UV-Vis spectroscopy.
Fokendt et al investigated intermolecular exchanges on the keto-enol form of AA by using 1 H NMR spectroscopy in the gas and liquid phase at 445-373 K. According to their results, the enol form is stable and its concentration is higher in the gas phase than in the liquid phase [11]. Thermodynamic parameters of keto-enol forms for AA derived from a Van According to 1 H-NMR studies, thermodynamic results show that decreasing temperature ranges increase equilibrium constants and lead to a high enol content of acetylacetone which is energetically favored in all phases [11]. The vibration analyses and its deuterated analogues of acetylacetone have been assigned by Tayyari et al [18]. Deconvolutions of the infrared spectra were shown broad and strong band of acetylacetone and it's deuterated at 1600 cm -1 region. This is because of creating a strong hydrogen bond and relatively chelated ring which exist in enol form. In another study on AA molecule, Roy et al. [19], investigated and computed the possible structure for the transition state and the potential energy barriers for the interconversion between keto and enol. Furthermore, it was found that in the solution phase the ratio of the keto-enol forms depends on the solvent polarity. In polar solvents such as water and DMSO, the keto tautomer prevails due to the higher dipole moment of the keto form in polar solvents.
Belova et al. studied the structural properties of MAA by gas electron diffraction (GED), DFT, and IR spectroscopy. These results indicated a mixture of 80% enol form and 20% keto form [20]. According to DFT calculations, exists only one stable enol form [3,20] [20].
A measurable method combined experimental-computational approach (CECA) [21], which provided accurate results cheaper and faster than other methods, has been established and is useful for the detection of tautomer ratios of EAA in solvents (acetonitrile, methanol, and chloroform). By using the MP2/cc-pVDZ and MP2/cc-pVTZ method the enol form percentage (6%) in acetonitrile and methanol solvent resulted. The extrapolation technique generates the enol ratio (10%) in the chloroform, and then the results are obtained using the MP2/cc-pVDZ (13%) and MP2/cc-pVTZ (11%) basis sets in chloroform. The theoretical data indicates similar results to experimental studies, for the solvent ' s ability in the stabilization of enol tautomer (Gas>CHCl3>MeOH>CH3CN) [21]. FT-IR is a very useful device that makes active almost all the organic molecules in the IR range. The FT-IR spectrum in the solvents shows two bands for keto form (symmetric and asymmetric C=O stretching bands) at about 1700 cm −1 and two bands for enol (C=O and C=C stretching bands) at about 1600 cm −1 [21]. are G 0 (g)=G 0 (keto)-G 0 (enol)=0.08 kcal.mol -1 , S 0 (g)=10.38 cal.mol -1 .K -1 , H 0 (g)=3.17 kcal.mol -1 in gas phase and G 0 (l)=-1.55 kcal.mol -1 , S 0 (l)=5.81 cal.mol -1 .K -1 , H 0 (l)=0.18 kcal.mol -1 in liquid phase. According to the upper obtained values, Keq and enol percentage could be calculated. According to 1 H NMR studies, thermodynamic results show that decreasing temperature ranges increases the equilibrium constants and causes a high enol percentage of EAA which is energetically preferred in all phases [11]. The data showed that in the gas phase of ethyl acetoacetate is the enol form more stable while it has little stability in the neat phase. However, the keto form is favored entropically in both phases [11].

Method of analysis
In this study, computational software including Gaussian 09 [27], Gauss View 5 [28], NBO 5.0 [29], and AIM2000 [30] programs were used for all the quantum calculations and investigation of the geometrical parameters of -ketoesters. All of the conformer's energies were calculated and compared with the most stable keto and enol conformer. The thermodynamic parameters of balanced keto-enol forms were calculated in the gas phase and solution phases including acetonitrile, carbon tetrachloride, and optimized by using B3LYP/6-311++G** levels [31]. Additionally, these parameters were calculated in solutions (C2H5OH, CCl4, and CH3CN) by using the SCRF-PCM method [32][33]. The electron charge density (ρ) and its Laplacian (∇ 2 ρ) were calculated by the AIM program to estimate the nature and strength of the IHB. In addition to bond order and Charge analysis calculations, the second-order interaction energies E (2) [34] were performed at the B3LYP/6-311++G** level using the NBO 5.0 program.

5.
Results and discussion

Tautomeric composition
Tautomeric equilibrium is one of the most important conversions in nature which has been studied by many researchers who investigated keto-enol tautomer in -ketoesters [3,7]. In this study, all stable enol forms are called "AU" and all stable keto forms are called "K" in ketoester compounds. Cis (I) and Trans (II) are isomeric enol tautomers. Also, in unsymmetrical -ketoesters compounds, Cis enol is more stable than Trans isomer due to the formation of the intramolecular hydrogen bonds. Figure 1 shows the keto-enol equilibrium in different -ketoesters. Due to the electronic properties and nature of the solvents, the ketoenol equilibrium position for the ketoesters is changed. As shown in Figure 2, to form an enolated species of -ketoesters type I, the most acidic proton is first eliminated from the C3 atom to give enolated type II. The negative charge could transfer to O1 (structure III) or O2 (structure IV). However, structure III is more favorable than structure IV because of the more positive charge at C2. As a result, AU-Enol is more stable than BU-Enol of -ketoesters as shown in Figure 1  In Table 1 were calculated in the gas phase and also in carbon tetrachloride and acetonitrile solvents.
The results show that the ratio of enol form in the polar solvent decreases and the probability of the presence of the keto form increases. In Table 1

Molecular geometry and intramolecular H-bond strength
The AIM topological parameters including EHB (hydrogen bond strength, kJ.mol -1 ), BCP (Bond Critical Point-charge density),  2 BCP (Bond Critical Point -Laplacian charge density) were obtained using AIM2000 software at the level of B3LYP/6-311++G (d, p). In addition, the relative Gilli's symmetry coordinates (Q, q1, q2, and ) were evaluated [35]. The obtained data are given in Table 2. Also, Table 2 is shown the geometrics effects of the studied ketoesters and compared them with AA, BAA, and EBA [4][5]18]. In Table 2 Higher values of q1, q2, Q, and lower values of  in -ketoesters compared to AA values demonstrate that these compounds have a weaker bond than AA. The results of Table 2 indicate that the strength of IHB of the studied molecules is as follows: AA> EMA> EBA> EAA ~ MAA ~ BAA. AA>EMA>EBA>BAA~EAA~MAA.
The stretching vibrations at 1600 cm -1 are assigned to the C=C, C=O stretching of the ketoester enol form, which are also coupled to OH and CH in-plane bending vibrations [18,21].
The symmetric and asymmetric stretching peaks of CH2 of keto forms in the -ketoesters are observed at high frequencies, as well as two strong peaks in the region of about 1700 cm -1 are related to stretching vibrations (C=O) of keto forms of -ketoesters [21,37].Also keto forms in the CH2 stretching region are not distinguishable in AA [36]. Usually, in the -ketoesters most of the frequencies generated in the keto form tend to be blueshift.

NBO analysis
Using the NBO 5.0 method at the level of B3LYP/6-311++G(d, p), The Wiberg bond orders, the Charge analysis, and the second-order energy between the occupied orbitals of one molecule and the unoccupied orbitals were investigated [29,34].

Wiberg bond orders
For comparison, the Wiberg bond orders [38] for both the most stable enol and keto forms of the -ketoesters are shown in Table 4. This table shows that the bond order of C3=C2 in the enol form of -ketoesters is significantly greater than that of AA. In addition, this Table   shows that the bond strength of C3-C4, O1-C2, O1…O2, and O2=C4 in the target molecules is shorter in comparison to AA in enol form. The O…H bond order of AA is higher than the -ketoesters, so the Wiberg bond order analysis confirms that the intramolecular hydrogen bond is weaker in -ketoesters [6,8]. On the other hand, the replacement of the R3 group with the ester groups prevents the separation of electrons in the C2=C3-C4=O2 of the chelate ring. As a result, in keto forms, the order of C=O bond in AA is higher relative to ketoesters compounds. Table 5 shows the charge distribution calculated by the NBO method for the optimal geometries of -ketoesters. The analysis of the data in Table 5 shows that the substitutions affect the charge distribution of carbon and oxygen atoms in (O1-C2=C3-C4=O2). The presence of an electron-donating group at the R3 position increases the positive charge around C4 and decreases the positive charge around C2. The outcomes presentation that by increasing the hydrogen acidity of the bridge from AA to -ketoesters, the hydrogen bond strength of the ester compounds is reduced [8].

Electron delocalization
In Table 6, the second-order calculated energy E (2) between the donor-acceptor orbitals in the different -ketoesters conformers and AA is listed. According to Table 6, the interaction between π*C4=O2 as the donor and π*C3=C2 as the acceptor has the highest energy in ketoesters. The results show that the second-order energies are reduced relative to AA due to the reduction of the electron location of the electrons in the chelate ring of esters, which corresponds to a decrease in the hydrogen bond strength of these compounds relative to AA.
Also, the energy of the interaction between π*C4=O2 and π*C3=C2 is almost the same in MAA, EAA, and BAA [8]. In EBA, this interaction increases due to the presence of phenyl substitution and the steric effect but in the molecule EMA, it reduces due to the presence of methyl substitution at -position and the steric effect [39]. On the other hand, the electrons interacting energies of LP(2)O1π*C2-C3, and LP(2)O2σ*O1-H1 in the esters are lower than AA, which is in accord with the decrease in the hydrogen bonding of the esters. The value of interaction energy for enol and keto tautomers in Table 6 shows LP2(O3)π*(C4-O2), LP1(O3)σ*(C4-O2) to are almost equal, which confirms the existence of both keto and enol tautomers in the studied compounds [8].  (2)O2σ*(C4-C3) indicate that these amounts in keto form are higher than that of the enol form, which can be deduced that the keto form is higher volume than the enol form.

UV-Visible spectra analyses
The UV absorption results including the calculated absorption wavelengths (λ), oscillator strengths (f), and experimental data, equilibrium constant (Keq), and ratio enol form of the title compounds calculated by TD-DFT/B3LYP/6-311++G(d, p) are given Table 7. These data can be related to their consistent molecular structure and electron transitions [40].
The theoretical and experimental electronic absorption spectra of the target molecules in acetonitrile, ethanol, and carbon tetrachloride solvents are reported in Table 7  The absorption maximum for AA has a wide peak in about 265 nm region, which is related to the chelating ring by the →* band transitions [40][41].While the absorption maximum and enol percentage of increases in non-polar solution [42]. In the gas and solvent phases, with increasing hydrogen bond strength, the absorption wavelengths have redshifts. Table 7 shows that the absorption spectra in polar solvent are about 200-260 nm and in non-polar solvent in the range 260-300 nm [43].
The results show that the max values in AU2 and K2 -ketoesters are very similar to AU1 and K1. So, wavelengths of AU2 and K2 are not reported in Table 7.
The theoretical and experimental results of UV analysis for EMA, MAA, and EAA the most stable keto-enol tautomerism show that in MAA, EAA, molecules, two peaks have been observed in the regions below 200 nm and above 220 nm, which are related to the keto form and the chelate ring in the enol form, respectively [44]. While in EMA due to the presence of methyl group at -position in the wavelengths were shifted to higher numbers (redshift).
The data in Table 7 for the BAA and EBA molecules show that both of them contain phenyl rings, that in the BAA molecule, the phenyl is attached to the ester group, while in the EBA molecule, the phenyl group is attached to the carbonyl. In the EBA, three bands of about 290, 240, and 200 nm have been observed experimentally and theoretically, which are assigned to the transfer of the phenyl group, the enol chelate rings, and the keto form, respectively. In BAA, only broad peak of about 230-300 nm [45] to the phenyl group and a bands at about 210 nm have been observed, which are related to the solvent cutoff. Also, no transfer band for enol form was observed in polar solvent because ratio the enol form is very low in NMR data [4]. However in the polar solvent, a strong pick has been demonstrated below 200 nm region which is related to the keto form.
The keto-enol equilibrium is very sensitive to the nature of the solvent. This means that in the carbon tetrachloride solvent it was focused to the enol adsorption band but in the acetonitrile solvent the keto adsorption band was distinguished. About the use of polar protic ethanol as solvent, it was observed that the keto intensity band is higher than the enol band [42,45].
The peaks observed in the about 200 nm region in Fig 3-4 are related to polar solvents that have a high absorption coefficient that indicates the keto shape in these solvents. The equilibrium constants obtained from UV in Table 7 and their Comparison with equilibrium constants via thermodynamics techniques in Table 1, it resulted that as the equilibrium constant values increases, the keto content rises. Therefore, in the gas and solution phase, the keto forms have more polarity than the enol forms, which is in good agreement with the reported results obtained from UV on the similar molecules [45].

Frontier molecular orbitals (FMO)
It is obvious that TD-DFT method are more likely to provide more HOMO→LUMO and HOMO-n→LUMO+n transition corresponds to the enol and keto forms, respectively. Also, the orbital transmission of HOMO→LUMO takes place at a wavelength of about 230 nm according to the theoretical calculations and at a wavelength of about 240 nm according to the experimental results in enol form of -ketoesters (Table 7). So these changes occurred towards higher wavelengths (red shift). In the keto form, a wavelength of about 200 nm was observed by the orbital transfer theory (HOMO-n→LUMO+n).
Frontier molecular orbital images for the two stable forms of keto and enol of the ketoesters and AA molecules are shown in Fig 6-7. According to this figure, the energy gap values in the keto and enol forms are about 6 and 5 eV, respectively. The low energy gap in the enol -ketoesters molecule means that enols are lower chemical reactivity and higher kinetic stability than keto form [47]. Also, the low energy gap in the enol means that it is softer than the keto form. A comparison of the experimental wavelengths and their HOMO-LUMO gaps in enol form shows that the wavelength is about 240 nm and is related to the envelope distance of about 5 eV. Also, the wavelength <200 nm is related to the gap value of about 6 eV of the keto shape, which confirms the presence of both enol and keto forms in the sample [48]. According to Table 1 and Table 7, the dipole moments are increased and the electronic gap (ΔE) between HOMO and LUMO are more in the keto form than in the enol form. According to NMR, UV-Vis, and FT-IR spectroscopy, both tautomers exist in -ketoesters molecules. The NMR results indicated that the AA molecule has a higher OH chemical shift (OH) than the -ketoesters. FT-IR spectroscopy showed that the OH stretching frequency in -ketoesters is higher, while the O…H and O…O bends stretching are observed at a lower frequency compared to AA. Besides, in the IR spectra, two strong peaks are seen at about 1700 cm -1 that is related to keto forms.

Conclusion
In the UV-Vis spectrum, two peaks have been observed in -ketoesters that show the presence of enol and keto forms, simultaneously. Also, equilibrium constants of solvents computed computationally and experimentally, show that the amount of enol form is reduced in both polar and nonpolar solvents. In addition, the results show that there is a higher probability of the presence of keto form in the solvents.  Table 1. Thermodynamic parameters for the most stable enol to keto tautomers of -ketoesters and AA compounds Table 2. The geometrical and topological parameters of the cis-enol forms of -ketoesters and AA compounds    Table. 6. Relevant second order perturbation energies E (2) (donor-acceptor) interactions of kcal.mol -1 in the most stable enol and keto forms of -ketoester and AA compounds. Table. 7. The experimental and B3LYP/6-311++G** calculated, wavelength (), oscillator strengths (f), and major contributions for stable keto and cis-enol forms of -ketoester compounds.     Enolization of β-ketoester The experimental UV-Vis spectra in CH3CN for β-ketoesters The experimental UV-Vis spectra in Ethanol for β-ketoesters The experimental UV-Vis spectra in CCl4 for β-ketoesters The HOMO and LUMO orbitals for cis-enol forms of β-ketoester and AA HOMO->LUMO

Figure 7
The HOMO and LUMO orbitals for keto forms of β-ketoester and AA HOMO-n->LUMO+n

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