Introduction

Lubricants are oils used to reduce wear and friction between mechanical parts in contact. Lubricants with additives can help make equipment last longer and use less energy [1]. The base oils are mixed with different kinds of additives to make lubricants with better oxidation stability, viscosity index, pour point, corrosion resistance, wear resistance, and rust resistance [2]. Multifunctional additives are components used to improve multiple lubricant properties simultaneously. Zinc-dialkyl dithiophosphate (Zn-DTPs) are widely used as anti-wear and antioxidants to prevent the corrosion of copper and lead additives [3-5]. Polyacrylates are applied as pour point depressants, anti-wear, and viscosity index improvers [6, 7].

Pyrano[2,3-d]pyrimidine derivatives are unsaturated, six-membered heterocycles created by the fusion of pyrimidine and pyran rings. Pyranopyrimidines are among the most important chemicals with various pharmacological effects, including anti-inflammatory [8], antibacterial [9-12], anti-cancer [13, 14], and antioxidant [15, 16] properties. Some pyrano[2,3-d]pyrimidine compounds were synthesized and applied as lubricant anti-oxidant additives [17]. Recently, novel pyranopyrimidine compounds were found to be effective multifunctional lubricant additives [18, 19]. Some derivatives were shown anti-corrosion activity with carbon steel [20, 21].

This work aims to synthesize new pyranopyrimidine derivatives using MgO-Nps and evaluate their usage as multifunctional additives for lubricants, such as anti-corrosion, anti-rust, and antioxidants.

Experimental

Chemicals and base oil

All the chemicals were supplied by BDH, Fluka AG, and Merck, and the nano-powder magnesium oxide was by Nanoshel. For the preparation of oil blend, base lubricating oils (Sixty stock) were blended with 1% weight/weight of each of the prepared derivatives. Table 1 lists the specifications of sixty stock base lubricating oils provided by the Midland Refineries Company in Baghdad, Iraq, and the test methods employed.

Table 1: Properties of base lubricating oils and the employed test methods

Instrumentation

The melting points were measured with the Stuart Electro-Thermal melting point apparatus (SMP1). Infrared spectra were recorded on a Shimadzu FTIR-8400S spectrophotometer in the form of a potassium bromide disk at the University of Baghdad-College of Science, Iraq. Proton nuclear magnetic resonance (1H-NMR) spectra were recorded on a Varian model UltraShield Plus at a frequency of 500 MHz, using the DMSO-d6 solvent at the University of Isfahan in Iran, and the chemical shifts were expressed in parts per million (ppm) relatives to an internal reference of tetramethylsilane (TMS).

The general method to synthesize pyranopyrazole, pyranopyrimidine, and chromene derivatives (1, 2, and 3)

A mixture of pyrrole-2-carboxaldehyde (1.0 eq., 1.90 g, 0.02 mol), malononitrile (1.0 eq., 1.32 g, 0.02 mol), and 3-methyl-1-phenyl-2-pyrazoline-5-one (1.0 eq., 3.48 g, 0.02 mol), 5,5-dimethyl-1,3-cyclohexandion (Dimedone) (1.0 eq., 2.80 g, 0.02 mol), or pyrimidine-2,4,6-trione (Barbituric acid) (1.0 eq., 2.56 g, 0.02 mol) in the presence of a catalyst of nano-powder magnesium oxide (0.25 eq., 0.20 g, 0.005 mol) in (20 mL) ethanol, was refluxed for 2-4 hours. The mixture was cooled at the end of reaction, and the formed precipitate was filtered and crystallized from ethanol to afford the title derivatives (1, 2, and 3) [22].

The general method to synthesize pyranopyrimidine derivatives (4, 5, and 6)

A mixture of an appropriate compound (1, 2, or 3) (1.0 eq., 0.01 mol) and isothiocyanatobenzene (1.2 mL, 0.01 mol, 1.0 eq.) in dimethylformamide (DMF) (10 mL) was heated for 6-8 hours. The produced solution was poured into ice to give the solid product which was filtered, and then crystallized from ethanol to obtain the title derivatives (4, 5, and 6) [23].

Some selected spectral data and physical properties for compounds (1-6)

Compound (1): 6-Amino-3-methyl-1-phenyl-4-(1H-pyrrol-2-yl)-1,4-dihydro-pyrano[2,3-c]pyrazolo-5-carbonitril

1 exhibits properties like yellow crystals, m.p. = 120-122 °C, F.W= C₁₈H₁₅N₅O, M.W= 317.35 g/mole, reaction yield = 95%.

The FT-IR (KBr) (ν_max/ cm^-1) spectral data are: 3472, 3328 (NH₂), 3271 (N-H), 3105 (C-H aromatic), 2981, 2839 (C-H aliphatic), 2195(CN), 1657 (C=N), and 1580 (C=C).

The ¹H-NMR chemical shifts (δ_H, in ppm): 13.7 (1H, singlet, N-H), 7.7-7.9 (5H, multiplet, Ar-H), 7.6 (1H, doublet, J=7.5 Hz, pyrrol), 7.4 (1H, doublet, J=7.5 Hz, pyrrol), 7.2 (1H, triplet, J=7.5 Hz, pyrrol), 6.5 (2H, singlet, NH₂), 3.4 (1H, singlet, C-H pyran), and 2.4 (3H, singlet, CH₃).

Compound (2): 7-Amino-2,4-dioxo-5-(1H-pyrrol-2-yl)-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidin-6-carbonitril

Brown crystals of m.p.= 150-152 °C, F.W= C₁₂H₉N₅O₃, M.W = 271.24 g/mole, and yield= 86%.

The FT-IR (cm^-1) responses are: 3405, 3312 (NH₂), 3236 (N-H), 2199 (CN), 1700, 1691 (C=O), and 1597 (C=C).

The ¹H-NMR (δ_H, ppm) characteristics are: 12.8 (singlet, 1H, NH), 10.8, 10.9 (2H, singlet, 2NH), 7.3 (1H, doublet, J=7.5 Hz, pyrrol), 6.9 (1H, doublet, J=7.5 Hz, pyrrol), 7.1 (1H, triplet, J=7.5 Hz, pyrrol), 6.4 (2H, singlet, NH₂), and 3.5 (singlet, 1H, CH pyran).

Compound (3): 2-Amino-7-dimethyl-5-oxo-4-(1H-pyrrol-2-yl)-5,6,7,8-tetrahydro-chromen-3-carbonitril

3 is a solid compound of brown color, m.p.= 248-250 °C, F.W= C₁₆H₁₇N₃O₂, M.W= 283.33 g/mole, and yield = 92%.

FT-IR (cm^-1) spectral data of 3 are: 3430, 3335 (NH₂), 3247 (N-H), 2958, 2872 (C-H aliphatic), 2191 (CN), 1674 (C=O), and 1600 (C=C).

¹H-NMR (δ_H, ppm): 13.4 (1H, singlet, N-H), 7.6 (1H, doublet, J=7.5 Hz, pyrrol), 7.2 (1H, doublet, J=7.5 Hz, pyrrol), 6.9 (1H, triplet, J=7.5 Hz, pyrrol), 5.6 (2H, singlet, NH₂), 3.3 (1H, singlet, C-H pyran), 2.3 (2H, singlet, CH₂), 2.1 (2H, singlet, CH₂), and 1.4 (6H, singlet, 2CH₃).

Compound (4): 5-Amino-3-methyl-1,6-di-phenyl-4-(1H-pyrrol-2-yl)tetrahydro-pyrazolo [4',3':5,6]pyrano [2,3-d] pyrimidine-7(1H)-thione

Orange crystals of 4 has m.p of 166-168 °C, F.W = C₂₅H₂₀N₆OS, M.W = 452.54 g/mole, and reaction yield = 71%.

FT-IR (cm^-1): 3207 (NH), 3100 (C-H aromatic), 2980 (C-H aliphatic), 1652 (C=N), 1591 (C=C), and 1433 (C=S).

¹H-NMR (δ_H, ppm): 13.7 (1H, singlet, N-H), 9.8 (1H, singlet, N-H), 7.1-7.9 (13H, multiplet, Ar-H), 3.3 (1H, singlet, C-H pyran), and 2.3 (3H, singlet, CH₃).

Compound (5): 6-Imino-7-phenyl-5-(1H-pyrrol-2-yl)-8-thioxo-1,5,6,7,8,9-hexahydro-2H-pyrano[2,3-d:6,5-d'] di-pyrimidin-2,4(3H)-dione

5 has deep violet oily character, F.W= C₁₉H₁₄N₆O₃S; M.W= 406.42 g/mole; yield= 65%.

FT-IR (cm^-1): 3254 (N-H), 3107 (C-H aromatic), 1722, 1688 (C=O), 1610 (C=C), and 1415 (C=S).

¹H-NMR (δ_H, ppm): 12.7 (singlet, 1H, NH), 11.5 (singlet, 1H, NH), 10.8, 11.0 (2H, singlet, 2NH), 6.8-7.4 (8H, multiplet, Ar-H), and 3.8 (singlet, 1H, CH pyran).

Compound (6): 4-Imino-8,8-dimethyl-3-phenyl-5-(1H-pyrrol-2-yl)-2-thioxo-octa-hydro-6H-chromene [2,3-d] pyrimidines-6-one

The brown solid product of 6 has m.p. = 156-160 °C, F.W= C₂₃H₂₂N₄O₂S, M.W = 418.52 g/mole, and yield = 73%.

FT-IR (cm^-1): 3210 (N-H), 3038 (C-H aromatic), 2978 (C-H aliphatic), 1680 (C=O), 1648 (C=N), 1595 (C=C), and 1445 (C=S).

¹H-NMR (δ_H, ppm): 13.6 (1H, singlet, N-H), 9.8 (1H, singlet, N-H), 7.1-7.5 (8H, multiplet, Ar-H), 3.4 (1H, singlet, C-H pyran), 2.3 & 2.2 (4H, singlet, 2CH₂), and 1.0 (6H, singlet, 2CH₃).

Oil Blend Formulation

The blends of the prepared derivatives (1–6) with a concentration of 1% weight/weight were prepared by dissolving and mixing one gram of each derivative in 100 grams of base oil (60 stock) for one hour at 80˚C, followed by stirring for two hours at room temperature [24].

Results and Discussion

The pyranopyrimidine derivatives (4, 5, and 6) were prepared in two stages. The first stage included the preparation of compounds (1, 2, and 3) from a three-component, one-pot reaction. The reaction involved two steps. In the initial step, Knoevenagel condensation of pyrrole-2-carboxaldehyde with malononitril in the presence of nanoparticles of magnesium oxide as a catalyst produced an intermediate derivative of (2-((1H-pyrrol-2-yl)methylene)malononitrile), and then the second step included a reaction of intermediate with 3-methyl-1-phenyl-2-pyrazoline-5-on, or dimedon, or barbituric acid (Scheme 1) [22].

The second stage involved the cyclization reaction of compounds (1, 2, or 3) with isothiocyanatobenzene to produce the desired derivatives (4, 5, and 6). Schemes 1 and 2 represent each of these reactions and mechanisms (Scheme 2).

Scheme 1: The synthesis routes for the prepared derivatives

The prepared compounds were identified by FT-IR and ¹H-NMR spectroscopies.

The FT-IR spectra of compounds 1, 2, and 3 showed stretching bands of the amine groups at 3472, 3405, and 3430 cm^-1, respectively. Also, bands at 3328, 3312, and 3335 cm^-1 showed for asymmetric stretching and at 3328, 3312, and 3335 cm^-1 for symmetric, while the nitrile (CN) showed a band in the region of 2191-2199 cm^-1.

The thione group (C=S) in compounds 4, 5, and 6 displayed stretching bands at 1433, 1415, and 1445 cm^-1. Another significant point is the disappearance of any band for amine (NH₂) and nitrile (CN) groups in the FT-IR spectra of these compounds [25].

The ¹H-NMR spectrum (in ppm) of compound 1 (pyrano[2,3-c]pyrazol derivative) showed a singlet signal at δ13.7 for pyrrole N-H, multiplet signals at the region δ=7.7-7.9 for phenyl protons, while the pyrrole ring protons appeared as doublet signals at δ=7.6 and δ=7.4, and as triplet signal at δ=7.2. The singlet signals at δ=6.5, δ3.4, and δ=2.4 were assigned for NH₂, C-H pyran, and methyl protons.

The ¹H-NMR spectrum after cyclization with phenyl isocyanate for compound 4 (pyrazolo-pyrano[2,3-d] pyrimidine-thione derivative) showed the appearance of a singlet signal at δ9.8 for N-H, and no signal disappearance of NH₂ protons.

The structure of compound 2 (pyrano[2,3-d]pyrimidin derivative) was confirmed by ¹H-NMR, which showed singlet signals at δ12.8 for pyrrole N-H, δ10.8, and δ10.9 for pyrimidine ring 2N-H. The protons of pyrrole ring responded as doublet signals at δ 7.3 and δ 6.9, and a triplet signal at δ7.1. The singlet signals at δ6.4 and δ3.5 were assigned for NH₂ and C-H pyran, respectively.

After cyclization, the ¹H-NMR spectrum of compound 5 showed signal disappearance of NH₂ protons and appearance of a singlet signal at δ11.5 for C=N-H, and a multiplet signal at the region δ6.8-7.4 for aromatic protons [26].

The ¹H-NMR spectrum of compound 3 (tetrahydro-chromene derivative) exhibited a singlet signal at δ 13.4 for pyrrole N-H, while the pyrrole ring protons appeared as doublet signals at δ7.6 and δ7.2 and as triplet signal at δ6.9. The singlet signals at δ5.6, and δ3.3 were assigned for NH₂ and C-H pyran, respectively. While the protons for two methylene and two methyl groups appeared as doublet signals at δ2.3, δ2.1, and δ1.4, respectively.

The ¹H-NMR spectrum after cyclization with phenyl isocyanate for compound 6 (chromene [2,3-d] pyrimidine derivative) displayed the appearance of a singlet signal at δ9.9 for N-H, multiplet signal at the region δ7.1-7.5 for protons of phenyl group, and the disappearance of NH₂ protons signal [27].

Scheme 2: Formation mechanism using MgO-Nps catalyst

The effectiveness of synthesized compounds as anti-corrosion additives

The American Society of Testing and Materials (ASTM-D-130) method, which comprises dropping a copper strip in blended oil and heating it at 100 °C for about three hours, was used to test the activity of synthesized compounds’ blends as anti-corrosion. After the heating period, the Cu-strip was taken out, and tarnish level was measured using the color-match scale of ASTM classification [28, 29]. All the compounds were discovered to be effective anti-corrosion lubricants additives, causing only a slight tarnish (1b), as opposed to a significant moderate tarnish (2a) on the blank.

The effectiveness of synthesized compounds as antirust additives

In the American Society of Testing and Materials (ASTM-D-665) procedure, a steel rod was dipped into a sample of blended oil mixed with water before being heated for four hours at 60 °C. This method was used to assess the anti-rust capabilities of blends of synthetic derivatives. Next, the test rod was checked for rust indicators. This test was conducted twice, and for it to be deemed successful, both test rods needed to be free of rust [30]. All synthetic derivative oil blends passed the rust-prevention test.

The effectiveness of synthesized compounds as antioxidant additives

Oil oxidation at high temperatures usually results in the formation of acidic components that cause sludge deposition, and metal corrosion. The Institute of Petroleum's (IP 280) testing method tested the oxidation stability of blended oils. This method has been utilized to determine the oxidation resistance under standard conditions of oxygen gas passing through an oil sample that has been mixed with an iron-copper metal catalyst for 72 hours at 120 °C [31]. Total sludge (T.S) and total acidity (T.A) levels in oil were determined after the period of the test was over, and the equation below was used to figure out the percentage of total oxidation products (TOP %):

Where, T.A denotes the total acidity in mg of KOH/g of oil, T.S is the total sludge in weight percentage, 56.1 represents the molecular weight of potassium hydroxide, and 180 is the mean molecular weight of oil oxidation acids. Figure 1 displays the results of the evaluation of oil blends. Accordingly, the findings show that all blends of synthetic derivatives 4, 5, and 6 have appropriate amounts of sludge and oxidation products and stronger oxidation stabilities than the base oil (blank). The oil blend with component 6 was about as stable against oxidation as the common antioxidant Hindered-Phenol derivative (HP) due to it structurally serves as a radical scavenger [32].

Figure 1: Graphical representation of total sludge, total oxidation products, and acidity of synthesized blended oils

Molecular docking study of synthesized compounds

Molecular docking is chosen to identify the interaction process and investigate potential binding simulations of the synthesized pyranopyrimidine derivatives 4, 5, and 6 on the active sites of two different proteins: rubredoxin (2DSX) from Desulfovibrio Gigas and cytochrome-c₃ (2CTH) protein from Desulfovibrio Vulgaris bacteria. These two kinds of Sulfate Reducing Bacteria (SRB) are types of Microbial Influenced Corrosion (MIC) in pipelines oil [33]. The crystal structures of 2DSX and 2CTH proteins were found in the protein data bank (PDB) of the Research Collaborator for Structural Bioinformatics (RCSB) [34] and were molecularly docked using the Auto Dock Vina program version 15.6. The synthesized pyrimidine derivatives 4, 5, and 6 displayed binding energies determined to be -6.6, -6.8, and -7.0 Kcal/mole, respectively, which were favorable docking scores for bonding interaction with the 2DSX receptor. While these derivatives possessed binding energies of -8.0, -6.8, and -6.8 Kcal/mole, respectively, showed good docking scores for bonding with the 2CTH receptor (a higher binding affinity was evident from more negative values of the binding energy). The docking outcomes are presented in Table 2.

Table 2: The molecular docking results of 4, 5, and 6 derivatives

The best binding of derivative pyrano[2,3-d] pyrimidine-7-thione (4) with the active site of the 2CTH receptor from Desulfovibrio Vulgaris bacteria with a binding energy of -8.0 Kcal/mole was achieved through different interactions. In detail, the thione group interacts with phenylalanine (PHE B: 76) by π -S. The two phenyl groups interact with histidine (HIS B: 35) by π - π T-shaped, lysine (LYS B: 75), alanine (ALA B: 62), and valine (VAL A: 86), respectively, by π -alkyl. On the other hand, the pyrrole ring interacts with aspartic acid (ASP A: 96) by π-anion. While the best binding of derivative chromene [2,3-d] pyrimidines-6-one (6) is with the active site of 2DSX receptor from Desulfovibrio Gigas bacteria, binding energy of -7.0 Kcal/mole was achieved through different interactions. For example, hydrogen bonds with tyrosine (TYR A: 11) and glutamic acid (GLU A; 12), the phenyl group interacts with glycine (GLY A: 10) by π- Amide stacked, and the pyrrole ring interacts with tyrosine (TYR A: 11) by π - π stacked.

Figures 2, 3, 4, 5, 6, and 7 depict two- and three-dimensional (2D and 3D) interactions to visualize the interactions of the synthesized pyrimidine derivatives 4, 5, and 6 with rubredoxin (2DSX) and cytochrome-c₃ (2CTH) proteins (Figures 2-7).

Figure 2: 2D and 3D interactions pose of derivative 4 with 2DSX protein

Figure 3: 2D and 3D interactions pose of derivative 5 with 2DSX protein

Figure 4: 2D and 3D interactions pose of derivative 6 with 2DSX protein

Figure 5: 2D and 3D interactions pose of derivative 4 with 2CTH protein

Figure 6: 2D and 3D interactions pose of derivative 5 with 2CTH protein

Figure 7: 2D and 3D interactions pose of derivative 6 with 2CTH protein

Conclusion

This work succeeded in synthesizing new efficient lubricant additives of pyranopyrimidine derivatives. Many tests have evidenced the multi-functionality of these additives as antioxidant, antirust, and anti-corrosion. Moreover, theoretical means have also proven the capability of these derivatives as microorganism-influenced corrosion inhibitors (MIC) against the Desulfovibrio Gigas bacteria and Desulfovibrio Vulgaris bacteria.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

HOW TO CITE THIS ARTICLE

Zainab A. K. Al-Messri. Synthesis, Characterization, and Effectiveness of Pyranopyrimidine Derivatives as Multi-function Additive for Lubricating Oils. Chem. Methodol., 2023, 7(8) 581-593

DOI: https://doi.org/10.22034/CHEMM.2023.393061.1669

URL: https://www.chemmethod.com/article_173035.html