Synthesis of new 1,2,3-triazole derivatives of uracil and thymine with potential inhibitory activity against acidic corrosion of steels

Article abstract of DOI:10.3390/molecules18044613

Ten 1,4-disubstituted 1,2,3-triazoles were synthesized from one of 1-(azidomethyl) benzene, 1-(azidomethyl)-4-fluorobenzene, 1-(azidomethyl)-4- chlorobenzene, 1- (azidomethyl)-4-bromobenzene or 1-(azidomethyl)-4-iodobenzene, generated in situ from sodium

Full text of DOI:10.3390/molecules18044613

Molecules 2013, 18, 4613-4627; doi:10.3390/molecules18044613
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis of New 1,2,3-Triazole Derivatives of Uracil and
Thymine with Potential Inhibitory Activity against Acidic
Corrosion of Steels
Guillermo E. Negrón-Silva 1,*, Rodrigo González-Olvera 1, Deyanira Angeles-Beltrán 1,
Nidia Maldonado-Carmona 1, Araceli Espinoza-Vázquez 1,2, 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.);
dab@correo.azc.uam.mx (D.A.-B.); ponque.chem@gmail.com (N.M.-C.);
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: 26 January 2013; in revised form: 11 April 2013 / Accepted: 16 April 2013 /
Published: 18 April 2013
Abstract: Ten 1,4-disubstituted 1,2,3-triazoles were synthesized from one of 1-(azido-
methyl)benzene, 1-(azidomethyl)-4-fluorobenzene, 1-(azidomethyl)-4-chlorobenzene, 1-
(azidomethyl)-4-bromobenzene or 1-(azidomethyl)-4-iodobenzene, generated in situ from
sodium azide and the corresponding benzyl halide, and dipropargyl uracil or dipropargyl
thymine. Optimal experimental conditions were established for the conventional click
chemistry. The corrosion inhibiting properties of some of these compounds, which were
determined by means of an electrochemical technique, are also presented.
Keywords: synthesis; triazoles; pyrimidines; biological; corrosion

Molecules 2013, 18
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1. Introduction
Corrosion problems have received considerable attention due to their detrimental effects on
materials that contribute to substantial economic losses and environmental pollution. The use of
organic inhibitors is one of the most practical and environmentally-friendly methods to protect metals
and alloys against corrosion, particularly at acid pHs that certainly damage the steel industrial
infrastructure, relevant to overall economic behaviour as one determinant factor of the GNP. A number
of heterocyclic organic compounds having either a delocalized set of electrons or just an electron pair
on nitrogen, oxygen or sulfur heteroatoms, through which they adsorb on metallic surfaces, can block
the active sites to decrease the rate of corrosion of steel, for example. Pyrimidines have various
pharmaceutical applications as analgesic, antipyretic, antihypertensive and anti-inflammatory drugs, in
pesticides, herbicides, plant growth regulators, and as organic calcium channel modulators [1–4]. A perusal
of the literature revealed that pyrimidine derivatives and the uracil and thymine nitrogen bases [5–16]
are efficient inhibitors to protect steel in acidic solutions [15,17]. 1,2,3-Triazoles have been the subject
of considerable research, mainly due to their usefulness in synthetic organic chemistry and also due to
their variety of interesting biological activities, forming part of the scaffolds of antibacterial and
antituberculosis agents [18,19], neuraminidase inhibitors [20], anticancer compounds [21–24], antiviral
agents [25–27], analgesic compounds [28], fungicidal activity [29–31], protein tyrosine phosphatase
inhibitors [32,33], and assorted biomolecules (nucleosides and nucleotides) [34,35]. On the other hand,
1,2,3-triazoles have other applications, like in chemosensors [36] and organocatalysts [37]. Just as
relevant to applications of 1,2,3-triazoles in the biological and pharmaceutical fields, these molecules
belong to the heterocyclic compounds class, constituting an important category of organic inhibitors
for corrosion protection of industrial alloys in different acidic solutions. Many substituted triazole
compounds continue to be of scientific and engineering interest, and thus they have been studied in
considerable detail as effective corrosion inhibitors for steel in acidic media [38–57]. In this context,
we decided to explore the synthesis of some new 1,2,3-triazoleuracils and 1,2,3-triazolethymines and
their anti-corrosion properties.
2. Results and Discussion
2.1. Synthesis
The dipropargyl uracil 3 was prepared from uracil (1) and propargyl bromide in the presence of
DBU by refluxing the mixture in acetonitrile for 18 h. The TLC (CH2Cl2/MeOH 95:5 v/v) for the crude
reaction mixture showed the formation of 3 (major product) and N-1-propargyluracil (minor product).
Scheme 1. Dialkylation of pyrimidine nucleobases 1–2 with propargyl bromide.
O
O
R
R
DBU (2.2 eq.)
HN
N
Br
+
CH3CN
O
N
H
O
N
(2.0 eq.)
reflux, 18 h
1
3
R = H ( )
R = H ( ), 79% yield
CH3 (2)
CH3 (4), 70% yield

Molecules 2013, 18
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The desired product 3 was obtained in 79% yield before purification by column chromatography
(Scheme 1). These same conditions were used for the preparation of 4, which was obtained in 70%
yield from thymine (Scheme 1). The second step of the synthesis was the preparation of 1,2,3-triazole
nucleobases 5–14 through a Huisgen cycloaddition reaction between azides and the terminal alkynes.
Based on the Fokin and Van der Eychen methodology [58], it was decided to carry out a
multicomponent Cu(I)-catalyzed click reaction for the preparation of the compounds [59–66]. Initially,
the reaction was tested by mixing dipropargyl uracil 3, benzyl chloride and sodium azide in the
presence of triethylamine and a catalytic amount of Cu(I) iodide [67–71], and stirring at room
temperature for 36 h, whereby compound 5 was obtained in 44% yield (Table 1, entry 1). When the
reaction was repeated using Cu(OAc)2•H2O as precatalyst [72–74], sodium ascorbate as reducing
agent, and 1,10-phenanthroline•H2O as ligand [67,75] in EtOH-H2O at room temperature, compound 5
was obtained in 74% yield (Table 1, entry 2). With these reaction conditions established, the remaining
compounds 6–14 were prepared and obtained in good yields (Table 1, entries 3–11).
Table 1. Multicomponent click reaction catalyzed by Cu(OAc)2•H2O.
O
NaN3
R1
O
N
N
H2O(5 mol%)
Cu(OAc)2
N
R1
N
1,10-Phen H2O (5 mol%)
N
N
O
N
+
X
EtOH-H2O (6:4)
Na ascorbate
r.t., 36 h
O
N
R2
N
N
R2
R2
3-4
5-14
R1 = H, Me
X = Cl, Br
R2 = H, F, Cl, Br, I
Entry
Compound
R1
R2
H
H
F
X
Yield a (%)
1 b
2
5
5
H
Cl
Cl
Cl
Cl
44
74
78
71
87
84
64
87
74
73
86
H
3
6
H
4
7
H
Cl
Br
I
5
8
H
Br
Br
Cl
Cl
Cl
Br
Br
6
9
H
7
10
11
12
13
14
CH3
CH3
CH3
CH3
CH3
H
F
8
9
Cl
Br
I
10
11
a Isolated yields after purification; b The reaction was carried out employing 0.53 mmol of 3, Cu(I) iodide (5 mol%),
and NEt3 (3 eq.), stirring at room temperature for 36 h.
1
13
The structure of all compounds was confirmed by examination of their H- and C-NMR spectra,
IR and mass spectra. The presence of the 1,4-disubstituted 1,2,3-triazole nucleobases was
unequivocally established by means of the characteristic chemical shift values of the triazolyl
hydrogens at 7.49–8.14 ppm and the chemical shift values for the carbon atoms of the triazole ring at
123.4–124.5 ppm for CH and 142.3–143.7 ppm for the quaternary carbon (Table 2). These chemical shift
values are completely consistent with those reported by Creary for 1,4-disubstituted 1,2,3-triazoles [76].

Molecules 2013, 18
Table 2. 1H- and 13C-NMR chemical shifts (ppm) of the triazole ring in compounds 5–14.
4616
Compound
R1
H
R2
H
F
H-5
C-5
C-4
5
6
7.49/7.62
7.96/8.12
7.98/8.14
7.98/8.13
7.95/8.12
7.49/7.62
7.96/8.12
7.50/7.64
7.50/7.65
7.95/8.11
123.4/123.7
124.0/124.3
124.2/124.5
124.2/124.5
124.1/124.5
123.5/123.7
124.0/124.3
123.5/123.7
123.5/123.7
124.1/124.4
142.3/143.4
143.0/143.4
143.0/143.4
143.0/143.4
143.0/143.4
142.6/143.5
143.1/143.5
142.8/143.7
142.8/143.7
143.1/143.5
H
7
H
Cl
Br
I
8
H
9
H
10
11
12
13
14
CH3
CH3
CH3
CH3
CH3
H
F
Cl
Br
I
2.2. Corrosion Inhibition Efficiencies
We evaluated, using electrochemical means, the corrosion inhibition efficiencies of the first four
compounds considered in this work. Figure 1 depicts, as an example, the impedance measurements for
both bare steel surfaces immersed in 1 M HCl (see Figure 1a), and the same system after adding
25 ppm of compound 3 to the acid media (see Figure 1b). The results of the analysis of the impedance
data are shown in Table 3. It is important to remark that all these compounds have corrosion inhibition
efficiencies, IE, close to 90% at a rather low concentration value.
Figure 1. Experimental impedance data, Nyquist plots, recorded in the systems a) API 5L
X52/1 M HCl and b) API 5L X52/1 M HCl + 25 ppm of compound 3.
12
40
b
32
a
8
24
16
4
8
0
0
0
30
60
90
120
150
180
0
10
20
30
40
Zre/cm2
Zre/cm2

Molecules 2013, 18
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Table 3. Electrochemical parameters obtained from experimental impedance data, see
Figure 1, including the corrosion inhibition efficiencies, IE.
Compound
Rs/Ω cm2
2.4
Rp/Ω cm2
30
C/µF
310
94
IE/%
-
Blank
1
2
3
4
2.5
242
88
7.1
304
97
90
2.0
163
167
100
82
1.8
233
87
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 are uncorrected. IR spectra were recorded on a Bruker Alpha FT-IR/ATR
13
spectrometer (Leipzig, Germany). NMR spectra (1H at 500 MHz, C at 125.76 MHz) were obtained
with a JEOL ECA-500 (500 MHz) spectrometer (Tokyo, Japan). Chemical shifts (δ) are given in ppm
downfield from Me4Si used as an internal reference; coupling constants are given in J (Hertz). High-
resolution mass spectra (HRMS) were recorded on a JEOL JMS-SX 102a and Agilent-MSD-TOF-
1069A spectrometers (Tokyo, Japan). The electrochemical impedance study was performed at room
temperature using the IM6-ZAHNER electrochemical workstation (ZAHNER-Elektrik 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 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 a steel sample of API 5L X52 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 inhibitor molecule. Simulation of the impedance data recorded
was conducted by means of electrical equivalent circuits [17] and the electrical parameters: Rs,
solution resistance, Rtc, charge transfer resistance and C, the capacitance, were obtained in this way.
3.2. Product Synthesis and Characterization
1,3-Di(prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione (3). In a 100 mL round-bottom flask containing a
magnetic stirrer and equipped with a reflux condenser, uracil (1, 1.12 g, 10 mmol) was suspended in
dry acetonitrile (15 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 3.3 mL, 3.35 g, 22 mmol) was
added and the mixture stirred for a few minutes until a clear solution was obtained. Subsequently,
propargyl bromide (80 wt. % in toluene, 2.22 mL, 2.97 g, 25 mmol) was added and the whole reaction
mixture was heated at reflux for 18 h. The acetonitrile was evaporated under vacuum and CH2Cl2 (20 mL)
was added. The organic phase was washed with aqueous NH4Cl solution (5%, 20 mL), dried with
anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by column
chromatography (CH2Cl2) and recrystallized from CH2Cl2/hexane (1:1 v/v) to obtain 1.48 g (79%

Molecules 2013, 18
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1
yield) of 3 as a white solid, m.p. 102–104 °C [Lit. [77] m.p. 105 °C]. H-NMR (CDCl3): δ = 2.17 (t,
J = 2.5 Hz, 1H, ≡C-H), 2.50 (t, J = 2.6 Hz, 1H, ≡C-H), 4.59 (d, J = 2.6 Hz, 2H, CH2), 4.68 (d, J = 2.5 Hz,
13
2H, CH2), 5.83 (d, J = 8.0 Hz, 1H, CH), 7.46 (d, J = 8.0 Hz, 1H, NCH). C-NMR (CDCl3): δ = 30.5
(CH2), 38.0 (CH2), 70.9 (≡C-H), 75.9 (C), 76.0 (≡C-H), 77.9 (C), 102.4 (CH), 140.8 (NCH), 150.5
(N2C=O), 161.7 (NC=O). FT-IR/ATR νmax cm−1: 3,289, 3,259 (≡C-H), 3,117, 3,090, 3,006, 2,983,
2,949, 2,124 (C≡C), 1,708 (C=C), 1,648 (NC=O, N2C=O), 1,540, 1,432. HRMS (ESI-TOF) calculated
for C10H8N2O2+H+: 189.0658; Found: 189.0661.
5-Methyl-1,3-di(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), DBU (3.3 mL, 22 mmol)
and propargyl bromide (80 wt. % in toluene, 2.22 mL, 25 mmol). The crude product was purified by
column chromatography (CH2Cl2) and recrystallized from CH2Cl2/hexane (1:1 v/v) to afford 1.41 g
(70% yield) of 4 as a white solid, m.p. 96–100 °C [Lit. [77] m.p. 101 °C]. 1H-NMR (CDCl3): δ = 1.97
(d, J = 1.3 Hz, 3H, CH3), 2.17 (t, J = 2.5 Hz, 1H, ≡C-H), 2.47 (t, J = 2.6 Hz, 1H, ≡C-H), 4.57 (d,
J = 2.6 Hz, 2H, CH2), 4.72 (d, J = 2.5 Hz, 2H, CH2), 7.26 (q, J = 1.2 Hz, 1H, NCH). 13C-NMR
(CDCl3): δ = 13.2 (CH3), 30.7 (CH2), 37.6 (CH2), 70.8 (≡C-H), 75.4 (≡C-H), 76.4 (C), 78.1 (C), 110.9
(CCH3), 136.8 (NCH), 150.4 (N2C=O), 162.6 (NC=O). FT-IR/ATR νmax cm−1: 3,274, 3,260 (≡C-H),
3,072, 2,985, 2,931, 2,128 (C≡C), 1,700 (C=C), 1,657 (NC=O), 1,628 (N2C=O), 1,463. HRMS (ESI-
TOF) calculated for C11H10N2O2+H+: 203.0815; Found: 203.0817.
1,3-Bis((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 (5 mg, 0.027 mmol, 5 mol%),
1,10-phenanthroline monohydrate (5 mg, 0.027 mmol, 5 mol%) and sodium L-ascorbate (107 mg,
0.54 mmol) in EtOH-H2O (6:4 v/v, 5 mL), followed by stirring for five minutes at room temperature.
Subsequently, 3 (100 mg, 0.53 mmol), sodium azide (76 mg, 1.17 mmol) and benzyl chloride (0.13 mL,
1.17 mmol) were added to the reaction mixture, which was stirred during 36 h at room temperature
(the product starts to precipitate after a few hours). Afterwards, H2O (15 mL) was added to the reaction
mixture to complete 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/EtOH 98:2 v/v) and recrystallized from CH2Cl2/hexane (1:1 v/v) to afford 180 mg (74% yield)
1
of 5 as a white solid, m.p. 171–172 °C. H-NMR (CDCl3): δ = 4.93 (s, 2H, CH2NC=O), 5.15 (s, 2H,
CH2NC=O), 5.43 (s, 2H, NCH2Ph), 5.47 (s, 2H, NCH2Ph), 5.69 (d, J = 7.9 Hz, 1H, CH), 7.20–7.28 (m,
4H, ArH), 7.32–7.42 (m, 6H, ArH), 7.44 (d, J = 8.0 Hz, 1H, NCH), 7.49 (s, 1H, ArH, triazole), 7.62 (s,
1H, ArH, triazole). 13C-NMR (CDCl3): δ = 36.2 (CH2NC=O), 44.2 (CH2NC=O), 54.2 (NCH2Ph), 54.4
(NCH2Ph), 102.0 (CH), 123.4 (ArCH, triazole), 123.7 (ArCH, triazole), 128.2 (2×ArCH), 128.4
(2×ArCH), 128.8 (ArCH), 129.0 (ArCH), 129.1 (2×ArCH), 129.3 (2×ArCH), 134.2 (Cipso), 134.6
(Cipso), 142.3 (Cipso, triazole), 142.6 (NCH), 143.4 (Cipso, triazole), 151.2 (N2C=O), 162.6 (NC=O).
FT-IR/ATR νmax cm1: 3,133, 3,067, 3,012, 2,954, 1,700 (C=C), 1,650 (NC=O, N2C=O), 1,555, 1,496,
1,452, 1,434. HRMS (ESI-TOF) calculated for C24H22N8O2+H+: 455.1938; Found: 455.1939.
1,3-Bis((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

Molecules 2013, 18
4619
monohydrate, and sodium L-ascorbate) was followed to obtain the compound 6, employing 3 (100 mg,
0.53 mmol), sodium azide (76 mg, 1.17 mmol) and 4-fluorobenzyl chloride (0.14 mL, 1.17 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 203 mg (78% yield) of 6 as a white solid, m.p. 186–188 °C.
1H-NMR (DMSO-d6): δ = 4.95 (s, 2H, CH2NC=O), 4.97 (s, 2H, CH2NC=O), 5.48 (s, 2H, NCH2Ph),
5.53 (s, 2H, NCH2Ph), 5.73 (d, J = 7.9 Hz, 1H, CH), 7.13–7.19 (m, 4H, ArH), 7.31–7.37 (m, 4H,
ArH), 7.80 (d, J = 7.9 Hz, 1H, NCH), 7.96 (s, 1H, ArH, triazole), 8.12 (s, 1H, ArH, triazole). 13C-NMR
(DMSO-d6): δ = 36.3 (CH2NC=O), 44.1 (CH2NC=O), 52.4 (NCH2Ph), 52.5 (NCH2Ph), 101.0 (CH),
116.0 (d, J2CF = 21.4 Hz, 2×ArCH), 116.2 (d, J2CF = 21.4 Hz, 2×ArCH), 124.0 (ArCH, triazole), 124.3
(ArCH, triazole), 130.8 (d, J3 = 8.8 Hz, 2×ArCH), 130.9 (d, J3 = 8.8 Hz, 2×ArCH), 132.6 (d,
CF
CF
J4CF = 2.5 Hz, Cipso), 132.8 (d, J4CF = 2.5 Hz, Cipso), 143.0 (Cipso, triazole), 143.4 (Cipso, triazole), 144.9
(NCH), 151.3 (N2C=O), 161.4 (d, JCF = 243.8 Hz, Cipso), 162.5 (NC=O), 163.4 (d, JCF = 243.8 Hz,
C
ipso). FT-IR/ATR νmax cm1: 3,126, 3,066, 3,012, 2,969, 1,705 (C=C), 1,657 (NC=O, N2C=O), 1,604,
1,544, 1,508, 1,453. HRMS (ESI-TOF) calculated for C24H20F2N8O2+H+: 491.1750; Found: 491.1751.
1,3-Bis((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, and sodium L-ascorbate) was followed to obtain compound 7, employing 3 (100 mg,
0.53 mmol), NaN3 (76 mg, 1.17 mmol) and 4-chlorobenzyl chloride (198 mg, 1.23 mmol). The crude
product was purified by column chromatography (CH2Cl2/EtOH 97:3 v/v) and recrystallized from
CH2Cl2/hexane (1:1 v/v) to afford 197 mg (71% yield) of the desired product 7 as a white solid, m.p.
185–187 °C. 1H-NMR (DMSO-d6): δ = 4.96 (s, 2H, CH2NC=O), 4.98 (s, 2H, CH2NC=O), 5.51 (s, 2H,
NCH2Ph), 5.55 (s, 2H, NCH2Ph), 5.73 (d, J = 7.9 Hz, 1H, CH), 7.28 (d, J = 8.4 Hz, 2H, ArH), 7.30 (d,
J = 8.3 Hz, 2H, ArH), 7.39 (d, J = 8.4 Hz, 2H, ArH), 7.40 (d, J = 8.4 Hz, 2H, ArH), 7.80 (d, J = 7.9 Hz,
13
1H, NCH), 7.98 (s, 1H, ArH, triazole), 8.14 (s, 1H, ArH, triazole). C-NMR (DMSO-d6): δ = 36.3
(CH2NC=O), 44.1 (CH2NC=O), 52.4 (NCH2Ph), 52.6 (NCH2Ph), 101.0 (CH), 124.2 (ArCH, triazole),
124.5 (ArCH, triazole), 129.27 (2×ArCH), 129.30 (2×ArCH), 130.46 (2×ArCH), 130.49 (2×ArCH),
133.38 (Cipso), 133.44 (Cipso), 135.4 (Cipso), 135.5 (Cipso), 143.0 (Cipso, triazole), 143.4 (Cipso, triazole),
144.9 (NCH), 151.3 (N2C=O), 162.6 (NC=O). FT-IR/ATR νmax cm1: 3,128, 3,064, 3,013, 2,970,
2,951, 1,702 (C=C), 1,655 (NC=O, N2C=O), 1,542, 1,491, 1,453. HRMS (ESI-TOF) calculated for
C24H20Cl2N8O2+H+: 523.1159; Found: 523.1158.
1,3-Bis((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 (100 mg, 0.53 mmol),
NaN3 (76 mg, 1.17 mmol) and 4-bromobenzyl bromide (292 mg, 1.17 mmol). The crude product was
purified by column chromatography (CH2Cl2/EtOH 97:3 v/v) and recrystallized from CH2Cl2/hexane
(1:1 v/v) to afford 288 mg (87% yield) of the desired product 8 as a white solid, m.p. 196–198 °C.
1H-NMR (DMSO-d6): δ = 4.96 (s, 2H, CH2NC=O), 4.98 (s, 2H, CH2NC=O), 5.49 (s, 2H, NCH2Ph),
5.53 (s, 2H, NCH2Ph), 5.73 (d, J = 7.9 Hz, 1H, CH), 7.21 (d, J = 8.4 Hz, 2H, ArH), 7.23 (d, J = 8.3 Hz,
2H, ArH), 7.53 (d, J = 8.3 Hz, 2H, ArH), 7.54 (d, J = 8.4 Hz, 2H, ArH), 7.80 (d, J = 7.9 Hz, 1H,
NCH), 7.98 (s, 1H, ArH, triazole), 8.13 (s, 1H, ArH, triazole). 13C-NMR (DMSO-d6): δ = 36.3

Molecules 2013, 18
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(CH2NC=O), 44.1 (CH2NC=O), 52.5 (NCH2Ph), 52.6 (NCH2Ph), 101.0 (CH), 121.9 (Cipso), 122.0
(Cipso), 124.2 (ArCH, triazole), 124.5 (ArCH, triazole), 130.76 (2×ArCH), 130.79 (2×ArCH), 132.21
(2×ArCH), 132.23 (2×ArCH), 135.8 (Cipso), 135.9 (Cipso), 143.0 (Cipso, triazole), 143.4 (Cipso, triazole),
144.9 (NCH), 151.2 (N2C=O), 162.5 (NC=O). FT-IR/ATR νmax cm1: 3,141, 3,128, 3,073, 1,703
(C=C), 1,656 (NC=O, N2C=O), 1,593, 1,543, 1,488, 1,455. HRMS (ESI-TOF) calculated for
C24H20Br2N8O2+H+: 611.0148; Found: 611.0150.
1,3-Bis((1-(4-iodobenzyl)-1H-1,2,3-triazol-4-yl)methyl)pyrimidine-2,4(1H,3H)-dione
(9).
The
procedure described above (using the same quantities of Cu(OAc)2•H2O, 1,10-phenanthroline mono-
hydrate, sodium L-ascorbate) was followed to obtain compound 9, employing 3 (100 mg, 0.53 mmol),
NaN3 (76 mg, 1.17 mmol) and 4-iodobenzyl bromide (365 mg, 1.23 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 315 mg (84% yield) of the desired product 9 as a white solid, m.p. 202–204 °C.
1H-NMR (DMSO-d6): δ = 4.95 (s, 2H, CH2NC=O), 4.97 (s, 2H, CH2NC=O), 5.46 (s, 2H, NCH2Ph),
5.50 (s, 2H, NCH2Ph), 5.73 (d, J = 7.9 Hz, 1H, CH), 7.06 (d, J = 8.2 Hz, 2H, ArH), 7.07 (d, J = 8.2 Hz,
2H, ArH), 7.69 (d, J = 8.2 Hz, 2H, ArH), 7.70 (d, J = 8.3 Hz, 2H, ArH), 7.79 (d, J = 7.9 Hz, 1H,
NCH), 7.95 (s, 1H, ArH, triazole), 8.12 (s, 1H, ArH, triazole). 13C-NMR (DMSO-d6): δ = 36.3
(CH2NC=O), 44.1 (CH2NC=O), 52.6 (NCH2Ph), 52.8 (NCH2Ph), 95.02 (Cipso), 95.08 (Cipso), 101.0
(CH), 124.1 (ArCH, triazole), 124.5 (ArCH, triazole), 130.81 (2×ArCH), 130.83 (2×ArCH), 136.2
(Cipso), 136.3 (Cipso), 138.06 (2×ArCH), 138.08 (2×ArCH), 143.0 (Cipso, triazole), 143.4 (Cipso
,
triazole), 144.9 (NCH), 151.2 (N2C=O), 162.5 (NC=O). FT-IR/ATR νmax cm1: 3,127, 3,074, 3,011,
2,944, 1,703 (C=C), 1,654 (NC=O, N2C=O), 1,588, 1,544, 1,484, 1,453. HRMS (ESI-TOF) calculated
for C24H20I2N8O2+H+: 706.9871; Found: 706.9851.
1,3-Bis((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 (4.5 mg,
0.025 mmol), 1,10-phenanthroline monohydrate (5 mg, 0.025 mmol), sodium L-ascorbate (99 mg,
0.5 mmol), 4 (100 mg, 0.49 mmol), NaN3 (70 mg, 1.08 mmol) and benzyl chloride (0.12 mL, 1.08 mmol).
The crude product was purified by column chromatography (CH2Cl2/EtOH 98:2 v/v) and recrystallized
from CH2Cl2/hexane (1:1 v/v) to afford 148 mg (64% yield) of the desired product 10 as a white solid,
m.p. 187–189 °C. 1H-NMR (CDCl3): δ = 1.86 (d, J = 1.0 Hz, 3H, CH3), 4.91 (s, 2H, CH2NC=O), 5.16
(s, 2H, CH2NC=O), 5.43 (s, 2H, NCH2Ph), 5.46 (s, 2H, NCH2Ph), 7.21–7.28 (m, 4H, ArH), 7.29 (d,
J = 1.1 Hz, 1H, NCH), 7.30–7.37 (m, 6H, ArH), 7.49 (s, 1H, ArH, triazole), 7.62 (s, 1H, ArH,
13
triazole). C-NMR (CDCl3): δ = 13.0 (CH3), 36.4 (CH2NC=O), 43.9 (CH2NC=O), 54.2 (NCH2Ph),
54.4 (NCH2Ph), 110.3 (CCH3), 123.5 (ArCH, triazole), 123.7 (ArCH, triazole), 128.2 (2×ArCH), 128.4
(2×ArCH), 128.8 (ArCH), 129.0 (ArCH), 129.1 (2×ArCH), 129.3 (2×ArCH), 134.3 (Cipso), 134.7 (Cipso),
138.7 (NCH), 142.6 (Cipso, triazole), 143.5 (Cipso, triazole), 151.2 (N2C=O), 163.5 (NC=O).
FT-IR/ATR νmax cm1: 3,133, 3,115, 3,068, 2,956, 1,697 (C=C), 1,672 (NC=O), 1,646 (N2C=O), 1,550,
1,496, 1,453, 1,432. HRMS (ESI-TOF) calculated for C25H24N8O2+H+: 469.2094; Found: 469.2096.
1,3-Bis((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 (4.5 mg,

Molecules 2013, 18
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0.025 mmol), 1,10-phenanthroline monohydrate (5 mg, 0.025 mmol), sodium L-ascorbate (99 mg,
0.5 mmol), 4 (100 mg, 0.49 mmol), NaN3 (70 mg, 1.08 mmol) and 4-fluorobenzyl chloride (0.13 mL,
1.08 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 216 mg (87% yield) of the desired product
1
11 as a white solid, m.p. 170–172 °C. H-NMR (DMSO-d6): δ = 1.77 (d, J = 1.0 Hz, 3H, CH3), 4.92
(s, 2H, CH2NC=O), 4.99 (s, 2H, CH2NC=O), 5.49 (s, 2H, NCH2Ph), 5.53 (s, 2H, NCH2Ph), 7.13–7.19
(m, 4H, ArH), 7.31–7.37 (m, 4H, ArH), 7.69 (d, J = 1.1 Hz, 1H, NCH), 7.96 (s, 1H, ArH, triazole),
8.12 (s, 1H, ArH, triazole). 13C-NMR (DMSO-d6): δ = 13.1 (CH3), 36.6 (CH2NC=O), 44.0
(CH2NC=O), 52.4 (NCH2Ph), 52.5 (NCH2Ph), 108.6 (CCH3), 116.0 (d, J2CF = 21.4 Hz, 2×ArCH), 116.2
(d, J2CF = 21.4 Hz, 2×ArCH), 124.0 (ArCH, triazole), 124.3 (ArCH, triazole), 130.8 (d, J3 = 8.8 Hz,
CF
2×ArCH), 130.9 (d, J3 = 8.8 Hz, 2×ArCH), 132.7 (d, J4 = 2.5 Hz, Cipso), 132.8 (d, J4 = 2.5 Hz,
CF
CF
CF
Cipso), 140.7 (NCH), 143.1 (Cipso, triazole), 143.5 (Cipso, triazole), 151.1 (N2C=O), 161.4 (d, JCF = 245.1 Hz,
ipso), 163.3 (NC=O), 163.4 (d, JCF = 245.1 Hz, Cipso). FT-IR/ATR νmax cm1: 3,133, 3,073,
C
3,012, 2,954, 1,694, 1,664, 1,641, 1,605, 1,510, 1,463, 1,435. HRMS (ESI-TOF) calculated for
C25H22F2N8O2+H+: 505.1906; Found: 505.1916.
1,3-Bis((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 4.5 mg (0.025 mmol)
of Cu(OAc)2•H2O, 1,10-phenanthroline monohydrate (5 mg, 0.025 mmol), sodium L-ascorbate (99 mg,
0.5 mmol), 4 (100 mg, 0.49 mmol), NaN3, (70 mg, 1.08 mmol) and 4-chlorobenzyl chloride (184 mg,
1.14 mmol). The crude product was purified by column chromatography (CH2Cl2/EtOH 97:3 v/v) and
recrystallized from CH2Cl2/hexane (1:1 v/v) to afford 198 mg (74% yield) of the desired product 12 as
1
a white solid, m.p. 154–156 °C. H-NMR (CDCl3): δ = 1.87 (d, J = 1.1 Hz, 3H, CH3), 4.91 (s, 2H,
CH2NC=O), 5.17 (s, 2H, CH2NC=O), 5.41 (s, 2H, NCH2Ph), 5.44 (s, 2H, NCH2Ph), 7.17 (d, J = 8.5 Hz,
2H, ArH), 7.21 (d, J = 8.5 Hz, 2H, ArH), 7.29 (d, J = 1.1 Hz, 1H, NCH), 7.30 (d, J = 8.5 Hz, 2H,
ArH), 7.33 (d, J = 8.5 Hz, 2H, ArH), 7.50 (s, 1H, ArH, triazole), 7.64 (s, 1H, ArH, triazole). 13C-NMR
(CDCl3): δ = 13.0 (CH3), 36.3 (CH2NC=O), 44.1 (CH2NC=O), 53.4 (NCH2Ph), 53.6 (NCH2Ph), 110.3
(CCH3), 123.5 (ArCH, triazole), 123.7 (ArCH, triazole), 129.3 (2×ArCH), 129.5 (2×ArCH), 129.6
(2×ArCH), 129.7 (2×ArCH), 132.8 (Cipso), 133.1 (Cipso), 134.8 (Cipso), 135.1 (Cipso), 138.7 (NCH),
142.8 (Cipso, triazole), 143.7 (Cipso, triazole), 151.2 (N2C=O), 163.5 (NC=O). FT-IR/ATR νmax cm1:
3,142, 3,121, 3,068, 3,012, 2,955, 2,925, 1,693 (C=C), 1,662 (NC=O), 1,637 (N2C=O), 1,491, 1,462,
1,433. HRMS (ESI-TOF) calculated for C25H22Cl2N8O2+H+: 537.1315; Found: 537.1323.
1,3-Bis((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 (4.5 mg,
0.025 mmol), 1,10-phenanthroline monohydrate (5 mg, 0.025 mmol), sodium L-ascorbate (99 mg,
0.5 mmol), 4 (100 mg, 0.49 mmol), NaN3 (70 mg, 1.08 mmol) and 4-bromobenzyl bromide (270 mg,
1.08 mmol). The crude product was purified by column chromatography (CH2Cl2/EtOH 97:3 v/v) and
recrystallized from CH2Cl2/hexane (1:1 v/v) to afford 225 mg (73% yield) of the desired product 13 as
1
a white solid, m.p. 148–150 °C. H-NMR (CDCl3): δ = 1.87 (d, J = 1.2 Hz, 3H, CH3), 4.91 (s, 2H,
CH2NC=O), 5.16 (s, 2H, CH2NC=O), 5.39 (s, 2H, NCH2Ph), 5.42 (s, 2H, NCH2Ph), 7.10 (d, J = 8.6 Hz,
2H, ArH), 7.15 (d, J = 8.6 Hz, 2H, ArH), 7.29 (d, J = 1.2 Hz, 1H, NCH), 7.46 (d, J = 8.5 Hz, 2H,

Molecules 2013, 18
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ArH), 7.49 (d, J = 8.5 Hz, 2H, ArH), 7.50 (s, 1H, ArH, triazole), 7.65 (s, 1H, ArH, triazole). 13C-NMR
(CDCl3): δ = 13.0 (CH3), 36.3 (CH2NC=O), 44.1 (CH2NC=O), 53.5 (NCH2Ph), 53.7 (NCH2Ph), 110.3
(CCH3), 122.9 (Cipso), 123.2 (Cipso), 123.5 (ArCH, triazole), 123.7 (ArCH, triazole), 129.9 (2×ArCH),
130.0 (2×ArCH), 132.3 (2×ArCH), 132.4 (2×ArCH), 133.3 (Cipso), 133.7 (Cipso), 138.7 (NCH), 142.8
(Cipso, triazole), 143.7 (Cipso, triazole), 151.2 (N2C=O), 163.4 (NC=O). FT-IR/ATR νmax cm1: 3,139,
3,101, 3,069, 2,998, 2,953, 2,922, 1,693 (C=C), 1,661 (NC=O), 1,637 (N2C=O), 1,488, 1,462, 1,432.
HRMS (ESI-TOF) calculated for C25H22Br2N8O2+H+: 625.0305; Found: 625.0311.
1,3-Bis((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 (4.5 mg,
0.025 mmol), 1,10-phenanthroline monohydrate (5 mg (0.025 mmol), sodium L-ascorbate (99 mg,
0.5 mmol), 4 (100 mg, 0.49 mmol), NaN3 (70 mg, 1.08 mmol) and 4-iodobenzyl bromide (339 mg,
1.14 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 305 mg (86% yield) of the desired product
1
14 as a white solid, m.p. 229–231 °C. H-NMR (DMSO-d6): δ = 1.77 (s, 3H, CH3), 4.92 (s, 2H,
CH2NC=O), 4.99 (s, 2H, CH2NC=O), 5.46 (s, 2H, NCH2Ph), 5.50 (s, 2H, NCH2Ph), 7.06 (d, J = 7.7 Hz,
2H, ArH), 7.07 (d, J = 7.7 Hz, 2H, ArH), 7.68–7.71 (m, 5H, NCH, ArH), 7.95 (s, 1H, ArH, triazole),
8.11 (s, 1H, ArH, triazole). 13C-NMR (DMSO-d6): δ = 13.1 (CH3), 36.6 (CH2NC=O), 44.0
(CH2NC=O), 52.6 (NCH2Ph), 52.8 (NCH2Ph), 95.01 (Cipso), 95.07 (Cipso), 108.6 (CCH3), 124.1(ArCH,
triazole), 124.4 (ArCH, triazole), 130.81 (2×ArCH), 130.82 (2×ArCH), 136.2 (Cipso), 136.3 (Cipso),
138.05 (2×ArCH), 138.08 (2×ArCH), 140.7 (NCH), 143.1 (Cipso, triazole), 143.5 (Cipso, triazole), 151.1
(N2C=O), 163.3 (NC=O). FT-IR/ATR νmax cm1: 3,138, 3,119, 3,072, 2,957, 1,696, 1,640, 1,590,
1,555, 1,464. HRMS (ESI-TOF) calculated for C25H22I2N8O2+H+: 721.0028; Found: 721.0019.
4. Conclusions
Ten new triazole derivatives of the pyrimidine bases uracil and thymine which are potential
corrosion inhibitors of steel in acidic media were synthesized in good yields, employing a “click”
multicomponent reaction.
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 for the
distinction of their membership and the stipend received. We also wish to thank Rebeca Yépez for
technical assistance and Teresa Cortes for her help with NMR experiments.
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Sample Availability: Samples of the compounds 3–14 are available from the authors.
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