Multicomponent Click Synthesis of New 1,2,3-Triazole Derivatives of Pyrimidine Nucleobases: Promising Acidic Corrosion Inhibitors for Steel

A series of new mono-1,2,3-triazole derivatives of pyrimidine nucleobases were synthesized by one-pot copper(I)-catalyzed 1,3-dipolar cycloaddition reactions between N-1-propargyluracil and thymine, sodium azide and several benzyl halides. The desired heterocyclic compounds were obtained in good yields and characterized by NMR, IR, and high resolution mass spectrometry. These compounds were investigated as corrosion inhibitors for steel in 1 M HCl solution, using electrochemical impedance spectroscopy (EIS) technique. The results indicate that these heterocyclic compounds are promising acidic corrosion inhibitors for steel.

To continue with our project on the synthesis of organic inhibitors for acidic corrosion of steel grade API 5L X52 [29], a series of new 1,2,3-triazole derivatives of nucleobases which incorporate the known structural features of corrosion inhibitory activity such as pyrimidine nucleobases (uracil and thymine) [40], and the 1,2,3-triazole moiety [35][36][37][38][39] were synthesized. This class of nitrogen heterocyclic compounds is of particular interest because of their promising corrosion inhibitory activity.

Synthesis
Propargyl nucleobases 3-4 are accessible after just one preparation step starting from the corresponding uracil and thymine with propargyl bromide under basic conditions (K 2 CO 3 or DBU) [41][42][43] or employing bis(trimethylsilyl)pyrimidine nucleobase [44][45][46]. Due to the feasibility of performing selective alkylation at N-1, the propargylation of bis(trimethylsilyl)pyrimidine method was selected to prepare compounds 3-4. Thus, uracil was treated with N,O-bis-(trimethylsilyl)acetamide (BSA) and propargyl bromide in dry acetonitrile under different conditions. Stirring the reaction mixture for 11 days at room temperature provided the desired product 3 in low yield (20%). When refluxing in dry CH 3 CN for 3 h was attempted, the TLC (CH 2 Cl 2 /MeOH, 95:5 v/v) showed a mixture of N-1-propargyluracil 3 and 1,3-dipropargyluracil. The optimum conditions for the propargylation reaction involved stirring at 45 °C for 72 h. Here, the 1,3-dipropargyl uracil was not observed in the reaction (TLC) and the desired product 3 was obtained in 64% yield after workup and purification by recrystallization (Scheme 1). Similarly to 3, the desired product N-1-propargylthymine 4 was prepared and isolated in 87% yield (Scheme 1).
The signals of the aromatic carbons in compounds 6 and 11 can be readily assigned based on their J CF coupling constants (Tables 2 and 3). For example, the 13    From these figures it is noted that the spectra obtained after addition of organic molecules to the corroding media increased the impedance (Z re ) value, and that in most of the cases they are characterized by two semicircles or two time constants, one constant at high frequency and the other at low frequency, which are generally attributed to the adsorption of the organic molecules onto the metal surface. The impedance parameters determined from the corresponding Nyquist diagrams are listed in Table 4. Inspection of Table 4 reveals that R ct values increase prominently, while C dl reduces with increasing concentrations of 1,2,3-triazole nucleobases 5-14. A large charge transfer resistance is associated with a slower corroding system. Furthermore, the smaller double layer capacitance, the better protection provided by an inhibitor. It is important to remark that all these compounds displayed corrosion inhibition efficiencies over 90% at rather low concentration values, which resulted even better than other types of corrosion inhibitors reported in the literature [30,[32][33][34][35][36][37][38][39]. All compounds studied in this work showed a corrosion inhibitive activity comparable at least or better than to other organic inhibitors derived from purine nucleobases (adenine and guanine) [53][54][55].

General
Commercially available reagents and solvents were used as received. Flash column chromatography was performed on Kieselgel silica gel 60 (230-400 mesh). Melting points were determined on a Fisher-Johns apparatus and were uncorrected. IR spectra were recorded on a Bruker Alpha FT-IR/ATR spectrometer (Leipzig, Germany). NMR spectra were obtained with JEOL ECA-500 (500 MHz) and JEOL Eclipse-400 (400 MHz) spectrometers (Tokyo, Japan). Chemical shifts (δ) are given in ppm downfield from Me 4 Si as an internal reference; coupling constants are given in J (Hertz). High-resolution mass spectra (HRMS) were recorded on JEOL JMS-SX 102a and Agilent-MSD-TOF-1069A spectrometers (Tokyo, Japan). Compounds 5 and 10 are known, however their spectroscopic data was not reported [56]. The electrochemical impedance study was performed at room temperature using the ZENNIUM-ZAHNER electrochemical workstation (ZAHNER-Electrik GmbH & Co.KG, Kronach, Germany), applying a sinusoidal ± 10 mV perturbation, within the frequency range of 100 KHz to 0.1 Hz to an electrochemical cell with a three-electrode setup. A saturated Ag/AgCl mini-electrode was used as reference, with a graphite bar as counter electrode, while the working electrode was the API 5L X52 steel sample with an exposed area of approximately 1 cm 2 , which was prepared using standard metallographic procedures. The corrosion inhibition efficiency (IE) was evaluated by means of electrochemical impedance spectroscopy (EIS) in the API 5L X52/1 M HCl system containing 0 (blank) or 25 ppm of the organic inhibitor. Simulation of the impedance data recorded was conducted by means of electrical equivalent circuits [40] and the electrical parameters: solution resistance (R s ), charge transfer resistance (R ct ), and double layer capacitance (C dl ) were obtained in this way.

Conclusions
The synthetic protocol for the preparation of N-1-propargylpyrimidine nucleobases has been optimized, these derivatives are important building blocks for the synthesis of many 1,2,3-triazoles of interest. Eight new 1,2,3-triazole derivatives of pyrimidine nucleobases were successfully synthesized in good yields through a one-pot three-component click reaction and fully characterized. The electrochemical study evidenced that these new class of heterocyclic compounds are promising corrosion inhibitors of steel in 1 M hydrochloric acid.