Multicomponent click synthesis of new 1,2,3-triazole derivatives of pyrimidine nucleobases: Promising acidic corrosion inhibitors for steel

Article abstract of DOI:10.3390/molecules181215064

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.

Full text of DOI:10.3390/molecules181215064

Molecules 2013, 18, 15064-15079; doi:10.3390/molecules181215064
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Multicomponent Click Synthesis of New 1,2,3-Triazole
Derivatives of Pyrimidine Nucleobases: Promising Acidic
Corrosion Inhibitors for Steel
Rodrigo González-Olvera 1, Araceli Espinoza-Vázquez 1,2, Guillermo E. Negrón-Silva 1,*,
Manuel E. Palomar-Pardavé 2, Mario A. Romero-Romo 2 and Rosa Santillan 3
1
Departamento de Ciencias Básicas, Universidad Autónoma Metropolitana, Av. San Pablo No. 180,
México D.F., C.P. 02200, Mexico; E-Mails: rogo@correo.azc.uam.mx (R.G.-O.);
arasv_21@hotmail.com (A.E.-V.)
2
Departamento de Materiales, Universidad Autónoma Metropolitana, Av. San Pablo No. 180,
México D.F., C.P. 02200, Mexico; E-Mails: mepp@correo.azc.uam.mx (M.E.P.-P.);
mmrr@correo.azc.uam.mx (M.A.R.-R.)
3
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto
Politécnico Nacional, Apartado Postal 14-740, 07000 México D. F., Mexico;
E-Mail: rsantill@cinvestav.mx
* Author to whom correspondence should be addressed; E-Mail: gns@correo.azc.uam.mx;
Tel.: +52-55-5318-9593; Fax: +52-55-5318-9000.
Received: 6 November 2013; in revised form: 30 November 2013 / Accepted: 2 December 2013 /
Published: 6 December 2013
Abstract: 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.
Keywords: nucleobases; multicomponent reaction; 1,2,3-triazoles; acidic corrosion; steel

Molecules 2013, 18
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1. Introduction
1,2,3-Triazoles are present in a number of compounds with assorted biological activities such as
anticancer, antibacterial, antifungal, anti-tubercular, and anti-HIV properties [1,2]. Nowadays, the
copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC, also known as the copper(I)-catalyzed
Huisgen-Meldal-Sharpless cycloaddition) is the most widely used method for the synthesis of
1,4-disubstituted 1,2,3-triazoles from a wide range of organic azides and terminal alkynes [3–7].
Moreover, this process allows for the assembly of complex molecules, thus generating new unknown
structures with an added potential biological and engineering value [8–10]. Monopropargyl pyrimidine
nucleobases (uracil and thymine) are versatile building blocks for the synthesis of biologically relevant
1,2,3-triazoles [11]. They are generally used as starting material for the synthesis of triazole
nucleosides [12–19], triazole nucleotides [20–23], oxiconazole analogues [24], nucleopeptides [25],
inhibitors of human topoisomerase type II [26], and nucleoamino oxyacids [27]. Further, these propargyl
nucleobases are also used in the synthesis of organogels [28], and as corrosion inhibitors [29]. In the last
years, the corrosion inhibition of steel in acid solutions by nitrogen-containing heterocyclic compounds
has been extensively studied. In this regard, 1,2,4-triazole derivatives are considered to be effective
acidic corrosion inhibitors [30–34]. Recently, some 1,2,3-triazole derivatives have been reported as a
new class of corrosion inhibitors in acidic media [35–39].
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 [35–39] were synthesized. This class of nitrogen
heterocyclic compounds is of particular interest because of their promising corrosion inhibitory activity.
2. Results and Discussion
2.1. 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 (K2CO3 or DBU) [41–43] or employing
bis(trimethylsilyl)pyrimidine nucleobase [44–46]. 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 CH3CN for 3 h
was attempted, the TLC (CH2Cl2/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).

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Scheme 1. Propargylation of pyrimidine nucleobases 1–2.
With compounds 3–4 in hand, we then performed a one-pot three-component 1,3-dipolar
cycloaddition reaction [47–50] to generate a series of 1,4-disubstituted 1,2,3-triazole nucleobases.
Based on our previously reported methodology [29,51], the reaction between monopropargyl
nucleobases 3–4, sodium azide, and several benzyl halides was carried out in the presence of a
catalytic amount of Cu(OAc)2·H2O in EtOH-H2O (2:1 v/v) at room temperature for 24 h to give the
desired products 5–14 in good yields (Table 1).
Table 1. One-pot three-component click reaction.
Entry
Compound
R1
H
R2
H
F
X
Yield a (%)
1
2
5
6
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
84
90
80
83
81
81
90
87
83
85
H
3
7
H
Cl
Br
I
4
8
H
5
9
H
6
10
11
12
13
14
CH3
CH3
CH3
CH3
CH3
H
F
7
8
Cl
Br
I
9
10
a Isolated yields after purification.
1
13
The structures of the prepared compounds were confirmed by H- and C-NMR spectroscopic
1
13
methods, and mass spectra. The H and C-NMR signals for 1,2,3-triazole nucleobases 5–14 were
assigned with the help of standard 2D heteronuclear correlation method (Tables 2 and 3). A singlet

Molecules 2013, 18
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1
observed in the H-NMR spectrum at δ = 8.10–8.13 ppm confirmed the presence of the triazolyl
hydrogen, supported by the signals in the 13C-NMR spectrum at δ = 124.1–124.3 ppm. The signals for the
quaternary carbon of the triazole ring appeared at δ =143.2–143.5 ppm in the 13C-NMR spectrum. These
chemical shift values are consistent with those reported for 1,4-disubstituted 1,2,3-triazoles [29,51,52].
The signals of the aromatic carbons in compounds 6 and 11 can be readily assigned based on their
13
JCF coupling constants (Tables 2 and 3). For example, the C-NMR spectrum for compound 6 shows
four doublets at 162.4, 116.1, 130.9, and 132.7 ppm with values of JCF = 244.0 (1J), 21.4 (2J), 8.8 (3J),
and 2.5 (4J) Hz, respectively.
Table 2. 1H, and 13C-NMR chemical shifts (ppm) for compounds 5–9 in DMSO-d6.
O
4
3
5
6
HN
5
R = H ( )
6
F ( )
O
N
2
1
8
7
Cl ( )
N
7
8
Br ( )
N
9
I ( )
12
13
N
9
11
R
10
14
13
12
3-H
5-H
5-C
[a]
6-H
6-C
7-H
7-C
9-H
10-H
12-H
12C
[a]
13-H 14-H
2-C
4-C
8-C
9-C
10-C 11-C
13-C
14-C
7.71 4.89
8.10
[a]
[a]
[a]
5
6
7
8
9
11.29
11.28
11.28
11.29
11.28
151.3
151.3
151.3
151.3
151.3
164.3 101.8 146.1 43.0 143.2 124.2
5.55 7.71 4.89 8.10
164.2 101.8 146.1 43.0 143.3 124.1
5.55 7.71 4.89 8.11
164.2 101.8 146.1 43.0 143.3 124.3
5.55 7.70 4.88 8.11
164.3 101.8 146.1 43.0 143.3 124.3
5.50 7.70 4.88 8.10
53.4
5.53
52.5
5.54
52.5
5.52
52.6
5.50
52.7
136.4 128.5
7.36
129.3 128.7
7.17 ---
116.1 162.4
7.40 ---
129.3 133.4
7.53 ---
132.2 122.0
132.7 130.9
7.30
135.4 130.5
7.23
135.8 130.8
7.08
7.70
---
164.3 101.8 146.1 43.0 143.2 124.3
[a] See Experimental section.
136.2 130.8
138.1
95.1
2.2. Corrosion Inhibition Efficiencies
The corrosion inhibitive efficiency, IE, of compounds 5–14 was examined by electrochemical
impedance spectroscopy. The blank’s response is shown in Figure 1(a). Note that its impedance
spectrum exhibited one single depressed semicircle, which indicates that the steel corrosion is mainly
controlled by a charge transfer process. In contrast, when compounds 5–14 are present (25 ppm), the
impedance spectra are characterized, in general, by two time constants (see Figure 1(b) and 1(c)).

Molecules 2013, 18
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From these figures it is noted that the spectra obtained after addition of organic molecules to the
corroding media increased the impedance (Zre) 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 Rct values increase prominently, while Cdl 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 [30,32–39]. 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) [53–55].
Table 3. 1H, and 13C-NMR chemical shifts (ppm) for compounds 10–14 in DMSO-d6.
3-H
6-H
6-C
7.59
7-H
7-C
4.85
8-H
8-C
1.71
10-H 11-H
10-C 11-C 12-C 13-C 14-C 15-C
8.10 5.54 [a] [a] [a]
53.3 136.5 128.5 129.3 128.7
5.53 7.36 7.17 ---
52.5 132.7 130.9 116.1 162.4
5.54 7.30 7.40 ---
52.5 135.5 130.5 129.3 133.4
5.55 7.26 7.561 ---
52.6 135.9 130.8 32.2 122.0
5.53 7.10 7.72 ---
52.8 136.2 130.9 138.1 95.1
13-H 14-H 15-H
2-C
4-C
5-C
9-C
10
11
12
13
14
11.28
11.27
11.27
11.30
11.29
151.2
151.2
151.2
151.3
151.3
164.8 109.4 141.8 42.8
7.58 4.85
164.8 109.4 141.7 42.8
7.59 4.85
164.8 109.4 141.7 42.8
7.61 4.87
164.8 109.4 141.8 42.8
7.60 4.87
164.8 109.4 141.7 42.8
[a] See Experimental section.
12.5 143.4 124.2
1.71 8.10
12.5 143.4 124.1
1.71 8.10
12.5 143.4 124.2
1.73 8.13
12.5 143.5 124.3
1.74 8.11
12.5 143.4 124.3

Molecules 2013, 18
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Figure 1. Experimental impedance data, Nyquist plots, recorded in the systems (a) API 5L
X52/1 M HCl, (b) API 5L X52/1 M HCl + 25 ppm of compounds 5-9, and (c) API 5L
X52/1 M HCl + 25 ppm of compounds 10–14.
(a)
(c)
(b)
Table 4. Electrochemical parameters obtained from experimental impedance data,
including the corrosion inhibition efficiencies (IE) at 25 ppm of the organic inhibitor.
Compound
Rs/Ω cm2
0.8
Rct/Ω cm2
30
Cdl/μF cm2
IE/%
---
Blank
5
310
39
43
50
18
70
19
29
56
54
49
2.5
435
93.1
95.6
95.9
96.1
92.9
90.2
95.0
95.0
95.0
94.9
6
1.3
681
7
1.1
725
8
1.0
770
9
1.7
425
10
11
12
13
14
1.5
306
1.4
600
1.4
599
1.5
600
1.3
588

Molecules 2013, 18
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3. Experimental
3.1. 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 Me4Si 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 cm2, 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 (Rs), charge
transfer resistance (Rct), and double layer capacitance (Cdl) were obtained in this way.
3.2. Product Synthesis and Characterization
1-(Prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione (3). In a 50 mL three-necked round-bottomed flask
equipped with a magnetic stirrer, a thermometer, and a reflux condenser, uracil (1, 1.12 g, 10 mmol)
was suspended in dry acetonitrile (15 mL), N,O-bis-(trimethylsilyl)acetamide (BSA, 6.12 mL, 25 mmol)
was added and the mixture stirred for a few minutes until a clear solution was obtained. Subsequently,
propargyl bromide (80 wt.% in toluene, 1.23 mL, 13.8 mmol) was added and the whole reaction
mixture was heated at 45 °C for 72 h. The acetonitrile was evaporated under vacuum and the residue
was treated with aqueous NH4Cl solution (5%, 20 mL) and extracted with CH2Cl2 in a continuous
liquid-liquid extractor for 12 h. The organic phase was dried with anhydrous Na2SO4 and concentrated
under vacuum. The crude product was purified by recrystallization from CH2Cl2/hexane (1:2 v/v) to
1
afford 0.96 g (64% yield) of 3 as a white solid, mp 164–166 °C [Lit. [43] mp 169–170 °C]. H-NMR
(DMSO-d6, 500 MHz): δ = 3.37 (t, J = 2.4 Hz, 1H, C≡C-H), 4.47 (d, J = 2.5 Hz, 2H, CH2), 5.59 (d,
13
J = 7.9 Hz, 1H, CH), 7.65 (d, J = 7.9 Hz, 1H, NCH), 11.33 (br, 1H, NH). C-NMR (DMSO-d6,
125.76 MHz): δ = 37.1 (CH2), 76.4 (≡C-H), 79.0 (C≡), 102.2 (CH), 145.0 (NCH), 150.9 (N2C=O),
164.1 (NC=O). FT-IR/ATR νmax cm−1: 3240 (≡C-H), 3114, 2990, 2907, 2860, 2806, 2117 (C≡C), 1750
(C=O), 1682 (C=O), 1617, 1456, 1408, 1380, 1328, 1239, 1174. HRMS (ESI-TOF) calculated for
C7H6N2O2 + H+: 151.0502; Found: 151.0503.

Molecules 2013, 18
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5-Methyl-1-(prop-2-ynyl)pyrimidine-2,4-(1H,3H)-dione (4). The procedure described above was
followed to obtain compound 4, employing thymine (2, 1.26 g, 10 mmol), BSA (6.12 mL, 25 mmol),
and propargyl bromide (80 wt.% in toluene, 1.23 mL, 13.8 mmol). The reaction mixture was heated at
60 °C for 72 h. The crude product was purified by recrystallization from CH2Cl2/hexane (1:2 v/v) to
afford 1.43 g (87% yield) of 4 as a white solid, mp 155–157 °C [Lit. [45] mp 157–158 °C]. 1H-NMR
(DMSO-d6, 500 MHz): δ = 1.72 (d, J = 0.9 Hz, 3H, CH3), 3.33 (t, J = 2.4 Hz, 1H, ≡C-H), 4.42 (d,
13
J = 2.5 Hz, 2H, CH2), 7.51 (d, J = 1.0 Hz, 1H, NCH), 11.35 (br, 1H, NH). C-NMR (CDCl3, 125.76
MHz): δ = 12.4 (CH3), 36.9 (CH2), 76.1 (≡C-H), 79.2 (C), 110.0 (CCH3), 140.7 (NCH), 150.9
(N2C=O), 164.7 (NC=O). FT-IR/ATR νmax cm−1: 3250 (≡C-H), 3154, 3088, 3012, 2932, 2892, 2831,
2123 (C≡C), 1701, 1649 (C=O), 1516, 1472, 1422, 1353, 1340, 1243, 1218, 1135. HRMS (ESI-TOF)
calculated for C8H8N2O2 + H+: 165.0658; Found: 165.0661.
1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4-(1H,3H)-dione (5). In a 50 mL round-bottomed
flask equipped with a magnetic stirrer, were added Cu(OAc)2·H2O (3.6 mg, 0.02 mmol, 5 mol%),
1,10-phenanthroline monohydrate (4 mg, 0.02 mmol, 5 mol%), and sodium L-ascorbate (59 mg, 0.3 mmol)
in EtOH/H2O (2:1 v/v, 3 mL), followed by stirring for five minutes at room temperature. Subsequently,
3 (60 mg, 0.4 mmol), sodium azide (29 mg, 0.44 mmol), and benzyl chloride (51 μL, 0.44 mmol) were
added to the reaction mixture which was stirred during 24 h at room temperature. Afterwards, H2O (10 mL)
was added to reaction mixture to induce precipitation of the product, which was filtered off, washed
with H2O, then with hexane and dried under vacuum. The crude product was purified by column
chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized from CH2Cl2/hexane (1:1 v/v) to afford
95 mg (84% yield) of 5 as a white solid, mp 215–217 °C. 1H-NMR (DMSO-d6, 500 MHz): δ = 4.89 (s,
2H, CH2NC=O), 5.53–5.57 (m, 3H, NCH2Ph, CH), 7.27–7.36 (m, 5H, ArH), 7.71 (d, J = 7.9 Hz, 1H,
13
NCH), 8.10 (s, 1H, ArH, triazole), 11.29 (br, 1H, NH). C-NMR (DMSO-d6, 125.76 MHz): δ = 43.0
(CH2NC=O), 53.4 (NCH2Ph), 101.8 (CH), 124.2 (ArCH, triazole), 128.5 (2×ArCH), 128.7 (ArCH),
129.3 (2×ArCH), 136.4 (Cipso), 143.2 (Cipso, triazole), 146.1 (NCH), 151.3 (N2C=O), 164.3 (NC=O).
FT-IR/ATR νmax cm−1: 3156, 3106, 3056, 2953, 2871, 2814, 1754, 1721, 1674, 1630, 1454, 1422.
HRMS (ESI-TOF) calculated for C14H13N5O2 + H+: 284.1142; Found: 284.1145.
1-((1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4(1H,3H)-dione (6). The procedure
described above (using the same quantities of Cu(OAc)2·H2O, 1,10-phenanthroline monohydrate,
sodium L-ascorbate) was followed to obtain compound 6, employing 3 (60 mg, 0.4 mmol), NaN3
(29 mg, 0.44 mmol), and 4-fluorobenzyl chloride (53 μL, 0.44 mmol). The crude product was purified
by column chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized from CH2Cl2/hexane (1:1 v/v)
1
to afford 108 mg (90% yield) of the desired product 6 as a white solid, mp 225–227 °C. H-NMR
(DMSO-d6, 500 MHz): δ = 4.89 (s, 2H, CH2NC=O), 5.53 (s, 2H, NCH2Ph), 5.55 (d, J = 7.9 Hz, 1H,
CH), 7.17 (t, J = 8.8 Hz, 2H, ArH), 7.36 (dd, J = 5.6, 8.5 Hz, 2H, ArH), 7.71 (d, J = 7.9 Hz, 1H, NCH),
8.10 (s, 1H, ArH, triazole), 11.28 (br, 1H, NH). 13C-NMR (DMSO-d6, 125.76 MHz): δ = 43.0
(CH2NC=O), 52.5 (NCH2Ph), 101.8 (CH), 116.1 (d, 2JCF = 21.4 Hz, 2×ArCH), 124.1 (ArCH, triazole),
130.9 (d, 3JCF = 8.8 Hz, 2×ArCH), 132.7 (d, 4JCF = 2.5 Hz, Cipso), 143.3 (Cipso, triazole), 146.1 (NCH),
151.3 (N2C=O), 162.4 (d, JCF = 244.0 Hz, F-Cipso), 164.2 (NC=O). FT-IR/ATR νmax cm−1: 3156, 3106,

Molecules 2013, 18
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3057, 2954, 2871, 2812, 1761, 1721, 1673, 1630, 1606, 1510, 1453. HRMS (ESI-TOF) calculated for
C14H12F1N5O2 + H+: 302.1048; Found: 302.1048.
1-((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4(1H,3H)-dione (7). The procedure
described above (using the same quantities of Cu(OAc)2·H2O, 1,10-phenanthroline monohydrate,
sodium L-ascorbate) was followed to obtain compound 7, employing 3 (60 mg, 0.4 mmol), NaN3
(29 mg, 0.44 mmol), and 4-chlorobenzyl chloride (74 mg, 0.46 mmol). The crude product was purified
by column chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized from CH2Cl2/hexane (1:1 v/v)
1
to afford 102 mg (80% yield) of the desired product 7 as a white solid, mp 222–224 °C. H-NMR
(DMSO-d6, 500 MHz): δ = 4.89 (s, 2H, CH2NC=O), 5.54 (s, 2H, NCH2Ph), 5.55 (d, J = 7.8 Hz, 1H,
CH), 7.30 (d, J = 8.7 Hz, 2H, ArH), 7.40 (d, J = 8.6 Hz, 2H, ArH), 7.71 (d, J = 7.9 Hz, 1H, NCH), 8.11
(s, 1H, ArH, triazole), 11.28 (br, 1H, NH). 13C-NMR (DMSO-d6, 125.76 MHz): δ = 43.0 (CH2NC=O),
52.5 (NCH2Ph), 101.8 (CH), 124.3 (ArCH, triazole), 129.3 (2×ArCH), 130.5 (2×ArCH), 133.4
(Cl-Cipso), 135.4 (Cipso), 143.3 (Cipso, triazole), 146.1 (NCH), 151.3 (N2C=O), 164.2 (NC=O).
FT-IR/ATR νmax cm−1: 3152, 3100, 3055, 2950, 2869, 2815, 1720, 1675, 1630, 1491, 1452, 831, 788.
HRMS (ESI-TOF) calculated for C14H12Cl1N5O2 + H+: 318.0752; Found: 318.0757.
1-((1-4-Bromobenzyl-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4(1H,3H)-dione (8). The procedure
described above (using the same quantities of Cu(OAc)2·H2O, 1,10-phenanthroline monohydrate,
sodium L-ascorbate) was followed to obtain compound 8, employing 3 (60 mg, 0.4 mmol), NaN3
(29 mg, 0.44 mmol), and 4-bromobenzyl bromide (110 mg, 0.44 mmol). The crude product was
purified by column chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized from CH2Cl2-Hexane
(1:1 v/v) to afford 120 mg (83% yield) of the desired product 8 as a white solid, mp 241–243 °C. 1H-NMR
(DMSO-d6, 500 MHz): δ = 4.88 (s, 2H, CH2NC=O), 5.52 (s, 2H, NCH2Ph), 5.55 (d, J = 7.9 Hz, 1H,
CH), 7.23 (d, J = 8.2 Hz, 2H, ArH), 7.53 (d, J = 8.2 Hz, 2H, ArH), 7.70 (d, J = 7.9 Hz, 1H, NCH), 8.11
(s, 1H, ArH, triazole), 11.29 (br, 1H, NH). 13C-NMR (DMSO-d6, 125.76 MHz): δ = 43.0 (CH2NC=O),
52.6 (NCH2Ph), 101.8 (CH), 122.0 (Br-Cipso), 124.3 (ArCH, triazole), 130.8 (2×ArCH), 132.2
(2×ArCH), 135.8 (Cipso), 143.3 (Cipso, triazole), 146.1 (NCH), 151.3 (N2C=O), 164.3 (NC=O).
FT-IR/ATR νmax cm−1: 3151, 3098, 3054, 2949, 2871, 2815, 1721, 1675, 1630, 1488, 1453, 1422, 831,
787. HRMS (ESI-TOF) calculated for C14H12Br1N5O2 + H+: 362.0247; Found: 362.0247.
1-((1-(4-Iodobenzyl)-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4-(1H,3H)-dione (9). The procedure
described above was followed to obtain compound 9, employing Cu(OAc)2·H2O (3.0 mg, 0.017 mmol),
1,10-phenanthroline monohydrate (3.4 mg, 0.025 mmol), sodium L-ascorbate (52 mg, 0.26 mmol), 3
(50 mg, 0.33 mmol), NaN3 (23 mg, 0.36 mmol), and 4-iodobenzyl bromide (113 mg, 0.38 mmol). The
crude product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized
from CH2Cl2/Hexane (1:1 v/v) to afford 110 mg (81% yield) of the desired product 9 as a white solid,
mp 259–261 °C. 1H-NMR (DMSO-d6, 500 MHz): δ = 4.88 (s, 2H, CH2NC=O), 5.50 (s, 2H, NCH2Ph),
5.55 (d, J = 7.9 Hz, 1H, CH), 7.08 (d, J = 8.2 Hz, 2H, ArH), 7.70 (d, J = 8.2 Hz, 3H, NCH, ArH), 8.10
(s, 1H, ArH, triazole), 11.28 (br, 1H, NH). 13C-NMR (DMSO-d6, 125.76 MHz): δ = 43.0 (CH2NC=O),
52.7 (NCH2Ph), 95.1 (I-Cipso), 101.8 (CH), 124.3 (ArCH, triazole), 130.8 (2×ArCH), 136.2 (Cipso),
138.1 (2×ArCH), 143.2 (Cipso, triazole), 146.1 (NCH), 151.3 (N2C=O), 164.3 (NC=O). FT-IR/ATR

Molecules 2013, 18
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ν
max cm−1: 3100, 3055, 2950, 2868, 2810, 1719, 1675, 1630, 1484, 1453, 1392, 831, 786. HRMS (ESI-
TOF) calculated for C14H12I1N5O2 + H+: 410.0108; Found: 410.0108.
1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-methylpyrimidine-2,4-(1H,3H)-dione (10). The procedure
described above was followed to obtain compound 10, employing Cu(OAc)2·H2O (4.0 mg, 0.022 mmol),
1,10-phenanthroline monohydrate (4.4 mg, 0.022 mmol), sodium L-ascorbate (65 mg, 0.33 mmol), 4
(70 mg , 0.43 mmol), NaN3 (31 mg, 0.47 mmol), and benzyl chloride (54 μL, 0.47 mmol). The crude
product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v) and recrystallized from
CH2Cl2/Hexane (1:1 v/v) to afford 103 mg (81% yield) of the desired product 10 as a white solid, mp
1
247–249 °C. H-NMR (DMSO-d6, 500 MHz): δ = 1.71 (d, J = 1.0 Hz, 3H, CH3), 4.85 (s, 2H,
CH2NC=O), 5.54 (s, 2H, NCH2Ph), 7.27–7.35 (m, 5H, ArH), 7.59 (d, J = 1.2 Hz, 1H, NCH), 8.10 (s,
13
1H, ArH, triazole), 11.28 (br, 1H, NH). C-NMR (DMSO-d6, 125.76 MHz): δ = 12.5 (CH3), 42.8
(CH2NC=O), 53.3 (NCH2Ph), 109.4 (CCH3), 124.2 (ArCH, triazole), 128.5 (2×ArCH), 128.7 (ArCH),
129.3 (2×ArCH), 136.5 (Cipso), 141.8 (NCH), 143.4 (Cipso, triazole), 151.2 (N2C=O), 164.8 (NC=O).
FT-IR/ATR νmax cm−1: 3121, 3078, 3026, 2836, 1685, 1644, 1441, 730, 705. HRMS (ESI-TOF)
calculated for C15H15N5O2 + H+: 298.1299; Found: 298.1301.
1-((1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylpyrimidine-2,4-(1H,3H)-dione (11). The
procedure described above was followed to obtain compound 11, employing Cu(OAc)2·H2O (3.0 mg,
0.018 mmol), 1,10-phenanthroline monohydrate (3.6 mg, 0.018 mmol), sodium L-ascorbate (53 mg,
0.27 mmol), 4 (60 mg, 0.37 mmol), NaN3 (27 mg, 0.41 mmol), and 4-fluorobenzyl chloride (49 μL,
0.41 mmol). The crude product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v)
and recrystallized from CH2Cl2-Hexane (1:1 v/v) to afford 104 mg (90% yield) of the desired product
1
11 as a white solid, mp 249–251 °C. H-NMR (DMSO-d6, 500 MHz): δ = 1.71 (d, J = 1.2 Hz, 3H,
CH3), 4.85 (s, 2H, CH2NC=O), 5.53 (s, 2H, NCH2Ph), 7.17 (t, J = 8.9 Hz, 2H, ArH), 7.36 (dd, J = 5.4,
8.8 Hz, 2H, ArH), 7.58 (d, J = 1.2 Hz, 1H, NCH), 8.10 (s, 1H, ArH, triazole), 11.27 (br, 1H, NH).
13C-NMR (DMSO-d6, 125.76 MHz): δ = 12.5 (CH3), 42.8 (CH2NC=O), 52.5 (NCH2Ph), 109.4
2
3
(CCH3), 116.1 (d, JCF = 22.6 Hz, 2×ArCH), 124.1 (ArCH, triazole), 130.9 (d, JCF = 8.8 Hz,
2×ArCH), 132.7 (d, 4JCF = 3.8 Hz, Cipso), 141.7 (NCH), 143.4 (Cipso, triazole), 151.2 (N2C=O), 162.4 (d,
JCF = 244.0 Hz, F-Cipso), 164.8 (NC=O). FT-IR/ATR νmax cm−1: 3175, 3110, 3063, 3046, 2811, 1681,
1644, 1603, 1509, 1462, 1214, 780, 758. HRMS (ESI-TOF) calculated for C15H14F1N5O2 + H+:
316.1204; Found: 316.1209.
1-((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylpyrimidine-2,4-(1H,3H)-dione (12). The
procedure described above was followed to obtain compound 12, employing Cu(OAc)2·H2O (3.0 mg,
0.018 mmol), 1,10-phenanthroline monohydrate (3.6 mg, 0.018 mmol), sodium L-ascorbate (53 mg,
0.27 mmol), 4 (60 mg, 0.37 mmol), NaN3 (27 mg, 0.41 mmol), and 4-chlorobenzyl chloride (69 mg,
0.43 mmol). The crude product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v)
and recrystallized from CH2Cl2-Hexane (1:1 v/v) to afford 105 mg (87% yield) of the desired product
12 as a white solid, m.p. 245–247 °C. 1H-NMR (DMSO-d6, 500 MHz): δ = 1.71 (s, 3H, CH3), 4.85 (s,
2H, CH2NC=O), 5.54 (s, 2H, NCH2Ph), 7.30 (d, J = 8.3 Hz, 2H, ArH), 7.40 (d, J = 8.4 Hz, 2H, ArH),
7.59 (s, 1H, NCH), 8.10 (s, 1H, ArH, triazole), 11.27 (br, 1H, NH). 13C-NMR (DMSO-d6, 125.76 MHz):

Molecules 2013, 18
15074
δ = 12.5 (CH3), 42.8 (CH2NC=O), 52.5 (NCH2Ph), 109.4 (CCH3), 124.2 (ArCH, triazole), 129.3
(2×ArCH), 130.5 (2×ArCH), 133.4 (Cl-Cipso), 135.5 (Cipso), 141.7 (NCH), 143.4 (Cipso, triazole), 151.2
(N2C=O), 164.8 (NC=O). FT-IR/ATR νmax cm−1: 3124, 3081, 3032, 2833, 1680, 1645, 1491, 1462, 1212,
779, 762. HRMS (ESI-TOF) calculated for C15H14Cl1N5O2 + H+: 332.0909; Found: 332.0911.
1-((1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylpyrimidine-2,4-(1H,3H)-dione (13). The
procedure described above was followed to obtain compound 13, employing Cu(OAc)2·H2O (3.0 mg,
0.018 mmol), 1,10-phenanthroline monohydrate (3.6 mg, 0.018 mmol), sodium L-ascorbate (53 mg,
0.27 mmol), 4 (60 mg, 0.37 mmol), NaN3 (27 mg, 0.41 mmol), and 4-bromobenzyl bromide (102 mg,
0.41 mmol). The crude product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v)
and recrystallized from CH2Cl2-Hexane (1:1 v/v) to afford 115 mg (83% yield) of the desired product
1
13 as a white solid, mp 245–247 °C. H-NMR (DMSO-d6, 400 MHz): δ = 1.73 (s, 3H, CH3), 4.87 (s,
2H, CH2NC=O), 5.55 (s, 2H, NCH2Ph), 7.26 (d, J = 7.7 Hz, 2H, ArH), 7.56 (d, J = 7.7 Hz, 2H, ArH),
13
7.61 (s, 1H, NCH), 8.13 (s, 1H, ArH, triazole), 11.30 (br, 1H, NH). C-NMR (DMSO-d6, 100.5
MHz): δ = 12.5 (CH3), 42.8 (CH2NC=O), 52.6 (NCH2Ph), 109.4 (CCH3), 122.0 (Br-Cipso), 124.3
(ArCH, triazole), 130.8 (2×ArCH), 132.2 (2×ArCH), 135.9 (Cipso), 141.8 (NCH), 143.5 (Cipso,
triazole), 151.3 (N2C=O), 164.8 (NC=O). FT-IR/ATR νmax cm−1: 3123, 3080, 3034, 2835, 1684, 1646,
1465, 1214, 762. HRMS (ESI-TOF) calculated for C15H14Br1N5O2 + H+: 376.0404; Found: 376.0407.
1-((1-(4-Iodobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylpyrimidine-2,4-(1H,3H)-dione (14). The
procedure described above was followed to obtain compound 14, employing Cu(OAc)2·H2O (2.7 mg,
0.015 mmol), 1,10-phenanthroline monohydrate (3.0 mg, 0.015 mmol), sodium L-ascorbate (46 mg,
0.27 mmol), 4 (50 mg, 0.30 mmol), NaN3 (21 mg, 0.33 mmol), and 4-iodobenzyl bromide (104 mg,
0.35 mmol). The crude product was purified by column chromatography (CH2Cl2/MeOH 90:10 v/v)
and recrystallized from CH2Cl2/Hexane (1:1 v/v) to afford 110 mg (85% yield) of the desired product
1
14 as a white solid, mp 238–240 °C. H-NMR (DMSO-d6, 400 MHz): δ = 1.74 (s, 3H, CH3), 4.87 (s,
2H, CH2NC=O), 5.53 (s, 2H, NCH2Ph), 7.10 (d, J = 7.9 Hz, 2H, ArH), 7.60 (s, 1H, NCH), 7.72 (d,
J = 8.2 Hz, 2H, ArH), 8.11 (s, 1H, ArH, triazole), 11.29 (br, 1H, NH). 13C-NMR (DMSO-d6, 100.5 MHz):
δ = 12.5 (CH3), 42.8 (CH2NC=O), 52.8 (NCH2Ph), 95.1 (I-Cipso), 109.4 (CCH3), 124.3 (ArCH,
triazole), 130.9 (2×ArCH), 136.2 (Cipso), 138.1 (2×ArCH), 141.7 (NCH), 143.4 (Cipso, triazole), 151.3
(N2C=O), 164.8 (NC=O). FT-IR/ATR νmax cm−1: 3161, 3136, 3088, 3040, 2821, 1684, 1648, 1464,
1216, 777, 759. HRMS (ESI-TOF) calculated for C15H14I1N5O2 + H+: 424.0265; Found: 424.0264.
4. 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.

Molecules 2013, 18
15075
Acknowledgments
The authors would like to thank Consejo Nacional de Ciencia y Tecnología, CONACyT (project
181448) for financial support. GENS, MEPP, MARR, and RS wish to acknowledge the SNI (Sistema
Nacional de Investigadores) for the distinction of their membership and the stipend received. We also
wish to thank Rebeca Yépez for her technical assistance, Teresa Cortez for her help with NMR
experiments, Delia Soto-Castro and Geiser Cuéllar for the mass measurements.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 3–14 are available from the authors.
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