Acetaldehyde–Ammonia Interaction: A DFT Study of Reaction

Article pubs.acs.org/JPCA

Acetaldehyde−Ammonia Interaction: A DFT Study of Reaction Mechanism and Product Identification Vera P. Tuguldurova,† Alexander V. Fateev,†,‡ Victor S. Malkov,† Oleg Kh. Poleshchuk,§ and Olga V. Vodyankina*,† †

National Research Tomsk State University, 36, Lenin Avenue, Tomsk 634050, Russia Tomsk State Pedagogical University, 60, Kievskaya Street, Tomsk 634061, Russia § National Research Tomsk Polytechnic University, 30, Lenin Avenue, Tomsk 634050, Russia ‡

S Supporting Information *

ABSTRACT: The product of acetaldehyde and ammonia reaction, namely, 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate, was synthesized and identified using a combination of experimental (NMR spectroscopy, IR spectroscopy, melting point determination) and DFT-based theoretical approaches. A reaction mechanism was proposed. The reaction was shown to proceed via the formation of aminoalcohol, imine, and geminal diamine intermediates accompanied by cyclization of these species. The calculation results allowed us to build a potential energy surface of the acetaldehyde and ammonia interaction and determine the most energetically favorable pathway to yield acetaldehyde ammonia trimer. The reaction product was found in an energy minimum (−53.5 kcal/mol).

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INTRODUCTION Today, nitrogen-containing organic heterocycles (e.g., pyridines, azoles, and others) are widespread and used in many applications. The basic way to synthesize these products is condensation of carbonyl compounds with ammonia, amines, and their derivatives taking place in the solution. Current experimental research is mostly focused on such interactions under conditions close to those in space (rarefied medium, gas phase, and low temperature).1−4 This is connected to possible reactions between the available carbonyl compounds and ammonia, which result in changing the chemical composition of stars, comets, and planets. These studies allowed identifying some intermediates (1-aminoethanol and ethanimine) due to their stabilization by formic acid and application of low temperatures.1,2 The known quantum-chemical calculations have tended to study the formaldehyde−ammonia interaction both in the gas phase at low temperatures3 and in aqueous solution.5 The potential energy surfaces of the hexamine formation mechanisms were calculated, and the pathways of reaction and transition states were determined. A mechanism of formaldehyde and ammonia interaction in aqueous solution at pH 7, which lies in a sequential chain extension to up to four N atoms required for cyclization into hexamethylenetetramine, was proposed by Kua et al.5 Both theoretical and experimental studies of the reaction at low temperatures and in the presence of formic acid3 showed that the hexamethylenetetramine is able to form under such conditions only through recyclization of trimethylenetriamine © 2017 American Chemical Society

stabilized by formic acid, accompanied by a release of two ammonia molecules. To the best of our knowledge, similar quantum-chemical studies have not been carried out for acetaldehyde. However, despite the similar structure of formaldehyde and acetaldehyde molecules, direct application of the formaldehyde model to describe a similar process with acetaldehyde is not possible due to the different properties of aldehydes. The nature of the hydration of short-chain aldehydes differs significantly due to the effect of the CH3 group on the acetaldehyde molecule. The change of the electron density distribution from formaldehyde to acetaldehyde decreases the hydration constant by a factor of 2000, according to Lewis and Wolfenden.6 This clearly demonstrated the significant differences in the chemistry of these compounds. Also, the formation of unbranched linear nitrogen−carbon chains is possible in the reaction of formaldehyde and ammonia, while in the acetaldehyde and ammonia reaction each stage is accompanied by a chain branching, which leads to inability to use the same approach as the one for formaldehyde. The first studies of the interaction of acetaldehyde with ammonia7,8 were carried out in the 1960s and the 1970s. The authors7 suggested that such interaction only resulted in the formation of 1-aminoethanol and described the mechanism of this reaction as an analog of the reaction of aromatic aldehydes Received: January 25, 2017 Revised: April 5, 2017 Published: April 5, 2017 3136

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25% aqueous ammonia solution at temperatures 260 K. The reactions of acetaldehyde condensation with ammonia and its derivatives occurring in solution at moderate temperatures are the basis for synthesizing a number of pharmaceuticals, dyes, insecticides, and other valuable products. Insights into the mechanism of interaction of a carbonyl compound and ammonia in solution are important for liquid-phase processes to obtain nitrogen-containing heterocyclic compounds that have a wide range of applications. The role of the solvent cannot be neglected because it may participate in the formation of the key intermediates. The product of acetaldehyde and ammonia condensation was synthesized in 1939.9 The final product was identified as a 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate (acetaldehyde ammonia trimer trihydrate).2,8,10,11

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COMPUTATIONAL DETAILS Geometry optimization of all the structures was performed using Gaussian 09 program package installed at the SKIF “Cyberia” supercomputer of Tomsk State University.13 Hybrid functional B3LYP14,15 and split-valence basis set with the addition of d-polarization functions for heavy atoms and pfunctions for hydrogen atoms 6-311G** were used. To determine the global minimum of the complicated molecules, a conformational analysis based on a molecular mechanics method with the force field of MM+ had been previously carried out. The geometry of the most stable conformers for each molecular structure was optimized in the gas phase. The values of the energy of the molecules in aqueous solution were obtained by reoptimization with the solvent by the PCM model. The vibrational frequencies were calculated to verify the absence of the imaginary vibrational frequencies. A scaling factor for vibrational frequencies was not used. To construct the potential energy surface (PES) of the system, the electronic energies of the optimized structures in solution were used. Each of these energies represents the sum of the electronic energy of the structure and its solvation energy including electrostatic and nonelectrostatic interactions and is designated Estructure. Corrections to zero-point energy, enthalpy, and Gibbs free energy were not included in Estructure. The energies of all structures in the solution, their numbering, and their positions on the reaction energy profile are shown in Table S1 in the Supporting Information. XYZ coordinates of all structures are represented in Table S3. The position of each structure on the PES is compared with the positions of the starting molecules (i.e., acetaldehyde, ammonia, and water). The position calculated of each subsequent intermediate on the reaction profile was the change in the energy of the stage with the addition of the value of the position of the previous intermediate. For example, structure 8 is formed from intermediate 7 as a result of the acetaldehyde molecule addition. The position of this structure 8 on the energy profile was calculated as

The first studies of this process and products and the structural characteristics of the product and its properties can be found elsewhere.7−12 However, the mechanism of this interaction in solution is a matter of discussion, and quantumchemical studies have not yet been performed. Thus the abovementioned published data, together with theoretical and experimental results of this work, will help us to determine the main pathways of acetaldehyde and ammonia reaction in solution.

Eposition(8) = Estructure(8) − (Estructure(7) + Estructure(CH3CHO)) + Eposition(7) = (− 312727.9) − ((− 216161.0) + (− 96558.4)) + (− 14.1) = − 22.7 kcal/mol

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These values are represented in Figure 4 as positions of the structures on the PES.

EXPERIMENTAL SECTION The 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate (acetaldehyde ammonia trimer trihydrate) was synthesized in a threenecked round-bottomed flask equipped with thermometer, dropping funnel, and magnetic stirrer according to the procedure.9 Acetaldehyde was slowly added to the flask with

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RESULTS AND DISCUSSION Identification Product. Because of the instability of 2,4,6trimethyl-1,3,5-hexahydrotriazine trihydrate, the reaction product was identified and its structure confirmed only by 3137

DOI: 10.1021/acs.jpca.7b00823 J. Phys. Chem. A 2017, 121, 3136−3141

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Figure 1. Side and top views of 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate optimized at B3LYP/6-311G** level of theory.

the NMR (NMR experimental data are presented in the Supporting Information) and IR spectroscopy. The melting point determined was compared with that of the commercial 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate. The melting point of the commercial sample was 93.7 °C (with decomposition), and that of the synthesized sample was 93.2 °C (with decomposition), which agrees well with the published Tm data (acetaldehyde ammonia trimer trihydrate) = 92−95 °C.11 The previous crystallographic studies10 of polycrystalline acetaldehyde ammonia trimer trihydrate showed that the hexagonal crystal unit cell contained six rings of trimers and three six-membered rings composed of water molecules, in which each ring composed of water molecules was located between the two rings of the trimer. In the present paper, geometry optimization of the molecular structure and calculation of vibrational frequencies were carried out to confirm the structure of the 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate. The unit cell of the acetaldehyde ammonia crystal, detected experimentally, contains 171 different atoms, which does not allow using such structure for the calculations. Therefore, in view of the stoichiometric coefficients and described “sandwich” structure of the trimer trihydrate, the molecule to optimize was modeled so that the three water molecules comprised a six-membered ring forming hydrogen bonds between themselves and with the nitrogen atoms of the trimer (Figure 1). XYZ coordinates of this structure are represented in Table S3 in the Supporting Information. Figure 2 shows the experimental and calculated IR spectra of the acetaldehyde ammonia trimer trihydrate. The experimental spectra are given for the resulting product and the commercial sample. The band assignment for these spectra and their comparison with the literature data12 are reported in Table S2 in the Supporting Information. The proof of the resulting compound structure is the almost complete agreement of the calculated and experimental data with the published data. The spectra contain characteristic absorption bands of the secondary amine (stretching and deformation vibrations at 3242 and 1500, 1305 cm−1, respectively); characteristic absorption bands of CH3 groups (ν (CH3) at 2979 cm−1; δ (CH3) at 1461 and 1450 cm−1); and vibrations of the C−H bonds (ν (CH) and δ (CH) at 2897 and 1371 cm−1, respectively). The bands of 1062−1115 cm−1

Figure 2. Experimental and calculated IR spectra of acetaldehyde ammonia trimer trihydrate.

indicate the presence of C−N bonds in the structure. Confirming the product structure showed that the acetaldehyde ammonia trimer can be formed from ammonia aqueous solution. It is noteworthy that the first three calculated band positions differ significantly from the experimental data, and they are responsible for the stretching vibrations of the O−H···N, NH, and O−H···O groups. All three bands are related to the vibrations of the bonds having a hydrogen atom. These absorption bands calculated using the B3LYP functional are typically overestimated by 150−250 cm−1. Some authors use different scaling factors for different ranges of frequency to cope with this. For example, 4000−2000 and 2000−500 cm−1, respectively, were scaled by a factor equal to the ratio of νexpOH/νharmOH = 0.9531 and νexpCO/νharmCO = 0.9818.16 In addition, the reason may be connected to the fact that the proposed location of water molecules in the theoretical model does not correspond to the location in the actual crystal. Because (O−H···O) band had the least consistency with the experimental data, it was not included in the correlation analysis. The graphs reflecting the correlation between the literature and the experimental vibrational frequencies and the correlation 3138

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interaction, we propose a scheme of the process leading to formation of 2,4,6-trimethyl-1,3,5-hexahydrotriazine (Figure 4). The reactants are located in the upper left corner, their energies in solution were taken as 0.00 kcal/mol, and all calculations were carried out with respect to these values. The diagram shows a chain growth in two directions: the number of carbon atoms increases from left to right and the number of nitrogen atoms increases downward, which occurs due to adding molecules of acetaldehyde and ammonia, respectively. The exceptions are the cyclization and dehydration reactions, which may be seen in all directions. For all structures, only their positions on the reaction PES are shown. To calculate the energy changes for each step, one needs to subtract the product level from the reagent level. For example, the interaction of diamine 6 with acetaldehyde results in the formation of aminoalcohol compound 7. The positions of diamine 6 and compound 7 on the PES are −8.6 and −14.1 kcal/mol, respectively, and the ΔE of this stage is −14.1 − (−8.6) = −5.5 kcal/mol. The addition of acetaldehyde is favorable; that is, the reactions occur with a decrease in energy when the secondary amines are formed. For example, the ΔE for the processes 1 → 2, 6 → 7, 7 → 8, 11 → 12, and 14 → 15 is equal to −11.0, −5.5, −8.6, −6.2, and −4.2 kcal/mol, respectively. It is noteworthy that the addition of acetaldehyde to a secondary aminecontaining oligomer to form a tertiary amine increases the energy of the system. Stages leading to the formation of structures 3, 9, and 13 have a ΔE of +1.9, +2.2, and +0.6 kcal/ mol, respectively. A slight increase in the energy of the system

between the calculated and experimental data are constructed on the basis of the data in Table S2 of the Supporting Information (Figure 3).

Figure 3. Correlation between the literature and experimental oscillation frequencies and the calculated and experimental values. R is the correlation coefficient, SD is the standard deviation, and N is the number of points.

The experimental spectrum is almost identical to the one reported in literature (R = 0.999). The calculated absorption bands are close to the experimental values (R = 0.993), which confirms the synthesized product structure and the adequacy of the selected level of theory. Results of the Investigation of the Reaction Mechanism. On the basis of the classical concepts and experimentally established intermediates1,2,8 of acetaldehyde and ammonia

Figure 4. Proposed mechanism of acetaldehyde−ammonia interaction. The energy values of the structure in solution as a position in the PES are marked in red (kcal/mol) above the corresponding structure. 3139

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crystallization is a 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate without oligomeric structure because no “extra” bands were found in the IR and NMR spectra of the acetaldehyde and ammonia reaction product. Thus the most energetically favorable pathway yielding the 2,4,6-trimethyl-1,3,5-hexahydrotriazine consists of the following steps. First, 1-aminoethanol 1 is formed by the reaction of acetaldehyde with ammonia and can be dehydrated to ethanimine or can add another aldehyde molecule. The stage of 1-aminoethanol 1 dehydration to imine 4 and further conversion of intermediate 2 to imine 5 are endergonic (ΔE (1 → 4) = +12.3 kcal/mol, ΔE (2 → 5) = +12.5 kcal/mol). However, the position of intermediate 4 on the PES is high (+2.5 kcal/mol). Moreover, dimeric structures 2 and 7 were observed experimentally.8 The formation of the dimeric structure 7 proceeds via the 1 → 2 → 5 → 7 stages, and the obvious pathway for its subsequent transformation is the 7 → 8 → 12 → 15 → 16 path yielding the desired product. Thus the most favorable pathway is the repeating of the following stages: addition of acetaldehyde to a primary amine group, dehydration to imine, and the addition of ammonia to form the geminal diamine.

is caused by the steric hindrance in the molecules of tertiary amines. We optimized structure 20 (XYZ coordinates of 20 are presented in Table S3), obtained by the addition of acetaldehyde to the secondary amino group in structure 9 to form a structure containing two tertiary amino groups. Its position on the PES was −16.1 kcal/mol (Table S1), which confirms our conclusion that the formation of only tertiary amine is not energetically favorable. (ΔE for the process 9 → 20 is equal to +4.4 kcal/mol.) The changes of the energies of dehydration of low- and highmolecular aminoalcohols to form the corresponding imines are always positive. In all cases, the system energy increases by 7.5−12.5 kcal/mol, therefore the formation of imines is less preferable and they are located at the upper borders of the reaction PES. The opposite effect is observed in the stages of ammonia addition to imines, yielding geminal diamines. Thus the system energy for stages 4 → 6, 5 → 7, 11 → 14, 12 → 15, and 17 → 18 is reduced by 11.1, 5.8, 10.3, 8.3, and 8.5 kcal/mol, respectively. The cyclization stages occurring with releasing one water molecule have energy effects close to zero (e.g., ΔE for stages 8 → 10 and 15 → 16 are +2.6 and −0.3 kcal/mol, respectively). The positions of the products of cyclization stages (structures 10 and 16) on the PES are equal to −20.1 and −21.4 kcal/mol, respectively. We mentioned that the addition of acetaldehyde to primary amine decreases the energy of the system in all cases. Thus it can be assumed that the most favorable transformation of the structure 15 (−21.1 kcal/mol on the PES) is the addition of another acetaldehyde molecule to the NH2 group to form oligomer 19 [HOCH(CH 3 )NHCH(CH 3 )NHCH(CH 3 )NHCH(CH 3 )OH]. We optimized this structure (XYZ coordinates of oligomer 19 are presented in Table S3 in the Supporting Information) and calculated its position on the PES of −31.1 kcal/mol (Table S1), which is lower than the position of structure 16 (−21.4 kcal/mol). It can be suggested that further oligomerization can occur in the solution, but the oligomeric structures were not detected by an analysis of the crystalline reaction product done according to the IR and NMR data in this study and by other authors.10,12 The above-mentioned structure of acetaldehyde ammonia reaction product is the acetaldehyde ammonia trimer stabilized by three water molecules. This structure lies at the level of −53.5 kcal/mol (not represented in the scheme). Other stable intermediates 8, 10, 15, and 19 (−22.7, −20.1, −21.1, and −31.1 kcal/mol) stabilized by three water molecules were also calculated. These structures (8·3H2O, 10·3H2O, 15·3H2O, and 19·3H 2 O, presented in Table S3 in the Supporting Information) were optimized, and their positions on the PES (Table S1 in the Supporting Information) were calculated. The positions were −44.7, −48.8, −46.8, and −53.0 kcal/mol, respectively. Thus the energy drop caused by the inclusion of three explicit water molecules in structures 8, 10, 15, and 19 was 22.0, 28.7, 25.7, and 21.9 kcal/mol, respectively. The stabilization of the product led to energy reduction by 32.1 kcal/mol. This energy reduction is due to the formation of hydrogen bonds between the structure and the water molecules. The molecule of acetaldehyde ammonia trimer coordinates a six-membered ring of three water molecules and thereby reduces its energy to a greater degree. Nevertheless, the actual product isolated from the reaction mixture by

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CONCLUSIONS An investigation of the acetaldehyde and ammonia reaction mechanism allows us to identify the main ways of managing the process and improving its efficiency (yield, energy, and economy). Understanding the main pathways of the interaction of acetaldehyde, ammonia, and water will develop the range of possible tools for external action on the formation of heterocyclic compounds. We can conclude: (1) 2,4,6-Trimethyl-1,3,5-hexahydrotriazine trihydrate (acetaldehyde ammonia trimer trihydrate) was synthesized. The structure was identified by NMR spectroscopy, IR spectroscopy, melting point determination, and quantum-chemical calculations. (2) The mechanism of the acetaldehyde and ammonia reaction was proposed, and analysis of intermediate locations on the reaction PES was carried out. We found the most energetically favorable pathway for the formation of acetaldehyde ammonia trimer. It consists of a sequential chain extension to up to three N atoms required for cyclization into acetaldehyde ammonia trimer. The chain extension contains the following repeating steps: addition of acetaldehyde to a primary amine group, dehydration to form imine, and the addition of ammonia to form the geminal diamine. (3) It was found that the acetaldehyde addition stage in the case of secondary amine formation leads to a decrease in energy of the system, while the addition of the aldehyde molecules to form tertiary amines increases it. (4) Aminoalcohol dehydration was found to be less preferable, while the addition of ammonia to imine reduced the system energy. (5) It was shown that the addition of the explicit water molecules decreases the energy of acetaldehyde ammonia trimer and the energies of the structures with positions on the PES close to the position of acetaldehyde ammonia trimer due to the formation of hydrogen bonds between the structure and the water molecules. (6) It was found that there is a thermodynamic possibility of forming oligomers with a chain length of more than three (−CH(CH3)NH−) units together with the formation of 3140

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(9) Lewis, D. T. The Kinetics of the Decomposition of AcetaldehydeAmmonia in Aqueous Acid Solution, and Some Notes on the Aldines. J. Chem. Soc. 1939, 968−972. (10) Lund, E. W. The Crystal Structure of Acetaldehyde-Ammonia. Acta Chem. Scand. 1958, 12, 1768−1776. (11) Nielsen, A. T.; Atkins, R. L.; Moore, D. W.; Scott, R.; Mallory, D.; LaBerge, J. M. The Structure and Chemistry of the Aldehyde Ammonias. 1-Amino-1-alkanols, 2,4,6-Trialkyl-1,3,5-hexahydrotriazines, and N,N′-Dialkylidene-1,1-diaminoalkanes. J. Org. Chem. 1973, 38, 3288−3295. (12) Novak, A. Infra-red Spectra of Acetaldehyde-Ammonia. Spectrochim. Acta 1960, 16, 1001−1009. (13) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; et al. Gaussian 09, revision C.01; Gaussian, Inc.: Wallingford, CT, 2010. (14) Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Slvetti Correlation Energy Formula into a Functional of the Electron Density. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789. (15) Becke, A. D. Density-functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648−5652. (16) Haupa, K.; Bil, A.; Barnes, A.; Mielke, Z. Isomers of the Acetic Acid−Water Complex Trapped in an Argon Matrix. J. Phys. Chem. A 2015, 119, 2522−2531.

acetaldehyde ammonia trimer. However, the analysis of the experimental data showed that only a 2,4,6-trimethyl-1,3,5hexahydrotriazine trihydrate is present in the crystalline products of the reaction. The study of the transition states and activation barriers of the proposed mechanism will provide a more detailed understanding of the reaction path.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.7b00823. NMR experimental data. Table S1. Electronic energy of the structures in solution and the PES position of all structures. Table S2. Comparison of experimental and calculated IR spectra with the literature data. Table S3. XYZ coordinates of the most stable structures. (PDF)

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AUTHOR INFORMATION

Corresponding Author

*Tel/Fax: +7 (3822) 20 04 19, E-mail: [email protected]. ORCID

Olga V. Vodyankina: 0000-0003-1221-8851 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Tomsk State University Competitiveness Improvement Program. We thank Jean Kollantai and Michael Salaev (Tomsk State University) for language review.

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REFERENCES

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