Copper-catalyzed synthesis and antimicrobial activity of disubstituted 1,2,3-triazoles starting from 1-propargyluracils and ethyl (4-Azido- 1,2,3-trihydroxybutyl)furan-3-carboxylate

Article abstract of DOI:10.1515/znb-2010-0110

1,3-Dipolar cycloaddition reactions of 1-propargyluracils 2a-h with the azido derivative 3 afforded the corresponding 1,2,3-triazoles 4a-h. Hydrazinolysis of the esters 4a-h gave the corresponding acid hydrazides 5a-h. Reaction of 5a-h with carbon disulfide in ethanol afforded 6a-h. The antimicrobial activity of compounds 4-6 was determined.

Full text of DOI:10.1515/znb-2010-0110

Copper-catalyzed Synthesis and Antimicrobial Activity of Disubstituted
1,2,3-Triazoles Starting from 1-Propargyluracils and Ethyl (4-Azido-
1,2,3-trihydroxybutyl)furan-3-carboxylate
Wael A. El-Sayeda and Adel A.-H. Abdel-Rahmanb
a Photochemistry Department, National Research Center, El-Dokki, Cairo, Egypt
b Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt
Reprint requests to Prof. Dr. Adel A.-H. Abdel-Rahman. Fax: +20-48-2235689.
E-mail: adelnassar63@hotmail.com or waelshendy@gmail.com
Z. Naturforsch. 2010, 65b, 57 – 66; received August 15, 2009
1,3-Dipolar cycloaddition reactions of 1-propargyluracils 2a – h with the azido derivative 3 af-
forded the corresponding 1,2,3-triazoles 4a – h. Hydrazinolysis of the esters 4a – h gave the corre-
sponding acid hydrazides 5a – h. Reaction of 5a – h with carbon disulfide in ethanol afforded 6a – h.
The antimicrobial activity of compounds 4 – 6 was determined.
Key words: 1,3-Dipolar Cycloaddition, 1,2,3-Triazoles, 1,3,4-Oxadiazoles, Antimicrobial Activity
Introduction
These materials have wide applications as fluorescent
probes and signaling units. Solid- phase synthesis of
1,2,3-triazolyl-uridines III from 5ꢀ-azidouridine and
monosubstituted and carboxy-substituted alkyne com-
ponents was reported by Epple et al. [26] (Fig. 1). On
the other hand, 1,3,4-oxadiazoles represent an impor-
tant class of compounds which possess a broad spec-
trum of biological activity in both agrochemicals and
pharmaceuticals, such as antibacterial [27], antimicro-
bial [28], insecticidal [29], herbicidal, fungicidal [30],
anti-inflammatory [31], hypoglycaemic [32], hypoten-
sion [33] characteristics, antiviral [34], and anti-tumor
[35]. Consequently, and as a part of our ongoing pro-
gram aiming at the synthesis of new antimicrobial
agents [36 – 39], we hypothesized that newly synthe-
sized compounds containing a 1,2,3-triazolyl moiety
linked through a trihydroxyalkyl chain of a substituted
furan (carbohydrate mimics) to a 1,3,4-oxadiazolyl
moiety can be expected to have enhanced biological
activities as antimicrobial agents.
The reaction of azides and alkynes yielding 1,2,3-
triazoles is the most popular Huisgen 1,3-dipolar cy-
cloaddition [1 – 3] and has found widespread appli-
cation, e. g., in combinatorial drug research and drug
discovery processes [4 – 7]. The application of azide-
alkyne cycloaddition as a common strategy to assem-
ble ligands in the construction of multivalent struc-
tures as an important principle used to increase weak
interactions to biologically relevant levels has been
reported [8 – 10]. Furthermore, 1,3-dipolar cycloaddi-
tion reactions have long been popular in the genera-
tion of carbohydrate mimetics [11] with thermally in-
duced Huisgen azide–alkyne cross-coupling [12] be-
ing used for the synthesis of N-glycosyl triazoles [13].
Triazole-substituted sugars have also been explored as
potential monovalent and multivalent galectin ligands
[14, 15] and for the investigation of substrate recog-
nition and inhibition of glycosyltransferases [16, 17].
The 1,2,3-triazole nucleus is found in a large num-
ber of compounds with agrochemical and pharmaceu-
tical uses [18], and shows activities, such as anti-HIV
[19] anti-microbial [20], antibacterial [21], and antitu-
Results and Discussion
The coupling reaction of uracils 1a – h with propar-
muor [22] properties and has also found many appli- gyl bromide was carried out as described in the litera-
cations in chemical industries [23]. Recently Zhou et ture for 2a, b at r. t. in DMF in the presence of sodium
al. [24] have reported the synthesis of 1,2,3-triazole- hydride to afford 1-propargyluracils2a – h in 75 – 85 %
substituted thymidines I which are found to be antivi- yields (Scheme 1). The analytical data of 2a and b
ral. Synthesis of triazole-linked heterocycle nucleoside are in agreement with those described in the literature
conjugates II was documented by Kosiova et al. [25]. [40]. The structure of 2c – h was based on their spec-
c
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
Fig. 1. 1,2,3-Triazoles linked to
carbohydrate mimics.
IR spectra of 4a – h showed characteristic absorption
bands at 1741– 1735 cm−1 and 1676– 1672 cm−1 for
the carbonyl-ester and carbonyl-amid functions, re-
spectively. The 13C NMR spectra of 4a, 4b, 4d and
4h showed the methyl group signal at δ = 15.20 –
15.24 ppm, the NCH2 signals at 46.95– 52.84 ppm and
the carbonyl groups at 164.21– 164.25 ppm. In addi-
tion, the mass spectra showed signals of the molecular
ion peaks which corresponded to the molecular formu-
las of 4a – h (Scheme 2).
1,2
a
R
H
Me
Br
F
1,2
e
R
NO2
CH2OMe
CH2O(CH2)4Me
CH2OBn
b
f
c
d
g
h
Hydrazinolysis of 4a – h by treatment with hy-
drazine hydrate in ethanol at reflux temperature af-
forded the corresponding hydrazides 5a – h in 84 –
91 % yields. The IR spectra of the products showed
absorption bands at 1676– 1682 cm−1 for carbonyl
Scheme 1. Synthesis of 1-propargyluracils.
tral data (IR, 1H, 13C NMR and mass spectra) as well
as elemental analyses. The 1H NMR spectra showed a
singlet peak at δ = 3.07 – 3.22 ppm corresponding to
the HC≡C proton in addition to a singlet at δ = 3.92 –
3.99 ppm for NCH2.
groups in addition to NH bands at 3362– 3370 cm−1
.
The 1H NMR spectra revealed the disappearance of the
ethyl signals, and instead signals appeared which cor-
respond to NH2 and NH groups (Scheme 2).
The recent advent of the Cu-catalyzed azide-alkyne
cycloaddition [41], one of the most reliable click
reactions [42], has enabled practical and efficient
preparation of 1,4-disubstituted 1,2,3-triazoles from
an unprecedented range of substrates. Thus, when
the alkynes 2a – h were treated with ethyl 5-(4-
azido-1,2,3-trihydroxybutyl)furan-3-carboxylate (3) in
When the hydrazide derivatives 5a – h were reacted
with carbon disulfide in the presence of potassium hy-
droxide in ethanol at reflux temperature, the corre-
sponding 1,3,4-oxadiazole derivatives 6a – h were af-
forded in 80– 91 % yields. The 13C NMR spectra of
6a, 6b, 6e and 6f showed a characteristic signal which
corresponds to C=S (Scheme 2).
◦
tBuOH at 0 C in the presence of 2,6-lutidine and
a catalytic amount of CuI, the corresponding 1,2,3-
triazoles 4a – h were obtained in 85 – 94 % yield. It
is believed that the starting point of the catalytic cy-
cle for the copper-catalyzed Huisgen reaction is con-
sidered to be the formation of a Cu–acetylide com-
plex [43, 44] which precludes alkynes as cycloaddition
partners to give the 5-cuprated 1,4-disubstituted 1,2,3-
triazole intermediate [45]. In general, no significant
difference of reactivity was observed when reacting 1-
propargyluracils 2a – h with the azide 3 at the reaction
times of 10 – 12 h for all derivatives, and no significant
differences in yields were observed.
Antimicrobial activity
The antimicrobial activity of compounds 4 – 6 was
evaluated against the three microorganisms Bacil-
lus subtilis (ATCC 6633) (Gram-positive), Pseu-
domonas aeruginosa (ATCC 27853) (Gram-negative),
and Streptomyces species (Actinomycetes). Each of
the test compounds and standards were dissolved in
12.5% DMSO at concentrations of 500 µg/mL. Fur-
ther dilutions of the compounds and standards in the
test medium were prepared at the required quantities.
Bacteria strains were supplied from the Botany Depart-
The structures of the 1,2,3-triazoles 4a – h were con- ment, Faculty of Science, Menoufia University, She-
firmed by their spectral and analytical data. Thus, the bin El-Koam, Egypt. The bacterial strains were main-
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
59
Scheme 2. Synthesis of
1,2,3-triazoles.
◦
tained on MHA (Mueller–Hinton agar) medium (Ox- at 37 C overnight. The inhibition zones were mea-
oid Chemical Co., UK) for 24 h at 37 ◦C. The medium sured after 24 h. The minimum inhibitory concentra-
was molten on a water bath, inoculated with 0.5 mL of tion (MIC) was defined as the intercept of the grave
the culture of the specific microorganism and poured of logarithm concentrations versus the diameter of the
into sterile Petri dishes to form a layer of about 3 – inhibition zones [47].
4 mm thickness. The layer was allowed to cool and
harden. With the aid of a cork-borer, cups of about
10 mm diameter were produced [46]. The activities
were evaluated using MHA medium (17.5 g casein hy-
drolysate, 1.5 g soluble starch, 1000 mL beef extract).
A stock solution of each compound (500 µg/mL) in
DMSO was prepared, and graded quantities of the test
compounds were incorporated in specified quantity of
sterilized liquid MH medium. Different concentrations
of the test compounds in DMF were placed separately
in cups in the agar medium. All plates were incubated
The values of minimal inhibitory concentrations
(MICs) of the tested compounds are presented in
Table 1. The results of the antimicrobial activity
test revealed that 5d, 6d and 6f showed the highest
activity against B. subtilis with MIC values of 75 µg
mL−1 followed by compounds 5f, 6c, 6d and 6h.
Compounds 6d and 6g showed the highest inhibition
activity against P. aeruginosa, whereas 5h, 6f and
6h were the most active among the series of tested
compounds against Streptomyces species with MIC
values of 75 µg mL−1. The results also revealed that
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
for dimethylsulfoxide solutions. 1H NMR spectra were deter-
mined with a Bruker AC-250 FT spectrometer. The chemical
shifts in ppm are expressed on the δ scale using tetramethyl-
silane as internal standard. Coupling constants are given in
Hz. Mass spectra were recorded on an AEIMS 30 spectrom-
eter. TLC was performed on Merck silica gel 60-F254 pre-
coated plastic plates. Microanalyses were performed in the
unit of microanalysis at Tokyo University (Japan). Antimi-
crobial activity of the synthesized compounds was examined
at the Botany Department, Faculty of Science, Menoufia Uni-
versity, Shebin El-Koam, Egypt.
Table 1. Minimum inhibitory concentration (MIC in
µg mL−1) of the title compounds. The negative control
DMSO showed no activity.
Compound Bacillus subtilis Pseudomonas
Streptomyces
species
aeruginosa
(Gram-positive) (Gram-negative) (Actinomycetes)
a
a
4a
4b
4c
4d
4e
4f
4g
4h
5a
5b
5c
5d
5e
5f
5g
5h
6a
6b
6c
6d
6e
6f
6g
6h
Penicillin
a
–
–
500
–
a
500
250
125
500
250
125
250
250
250
125
100
250
75
100
125
125
125
100
75
250
500
250
500
100
250
250
125
125
250
250
125
100
125
125
100
75
100
125
100
100
125
75
a
–
125
125
125
500
125
250
125
500
125
125
125
125
100
125
75
General procedure for the preparation of 1-propargyluracils
2a – h
A mixture of an uracil derivative 1a – h (10 mmol),
sodium hydride (0.288 g, 12 mmol), and dry DMF (20 mL)
◦
was stirred at r. t. for 15 min at 0 C, and the mixture was
stirred overnight at r. t. After filtration, the solvent was re-
moved in vacuo, and the residue was chromatographed on a
silica gel column, using 0.5 % MeOH in CH2Cl2 to afford
the propargylated products 2a – h in 75 – 85 % yield.
250
75
100
100
31
250
100
75
100
46
5-Bromo-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione (2c)
Yellow powder; m. p. 188 – 190 ◦C; yield: 1.74 g (76 %). –
IR (KBr): ν = 1668 (C=O), 3367 cm−1 (NH). – 1H NMR
([D6]DMSO): δ = 3.11 (s, 1H, HC≡C-), 3.98 (s, 2H,
NCH2), 8.11 (s, 1H, 6-H), 9.96 (brs, 1H, NH). – 13C
NMR ([D6]DMSO): δ = 35.80 (CH2), 76.65 (HC≡C), 81.25
(HC≡C), 104.18 (C-5), 149.50 (C-6), 153.68 (C-2), 158.88
(C-4). – MS (EI, 70 eV): m/z ( %) = 228/230 (82) [M]+. –
100
75
33
Totally inactive (MIC > 500 µgmL−1).
some compounds showed little or no activity against
the microorganisms (Table 1).
From the structure-activity relationship it is clear C7H5BrN2O2 (229.03): calcd. C 36.71, H 2.20, N 12.23;
found C 36.60, H 2.13, N 12.09.
that compounds containing the 1,2,3-triazolyl moiety
linked through a trihydroxy alkyl chain of a substituted
furyl ring (carbohydratemimics) to a 1,3,4-oxadiazolyl
moiety showed higher activity than the corresponding
furyl-substituted esters or hydrazide derivatives. Fur-
thermore, substitution at the 5-position in the uracil
ring with a fluorine atom enhances the antimicrobial
activity especially against B. subtilis and P. aerugi-
nosa, whereas the activity was reduced when the 5-
position was substituted with other groups. Moreover,
substitution at the 5-position with a methoxy methyl
group resulted in higher antimicrobial activity espe-
cially against B. subtilis and P. Streptomyes.
5-Fluoro-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione (2d)
Colorless powder; m. p. 169 – 171 ◦C; yield: 1.22 g
(73 %). – IR (KBr): ν = 1670 (C=O), 3359 cm−1 (NH). –
1H NMR ([D6]DMSO): δ = 3.07 (s, 1H, HC≡C-), 3.95 (s,
2H, NCH2), 8.07 (s, 1H, 6-H), 9.93 (brs, 1H, NH). – MS (EI,
70 eV): m/z (%) = 168 (75) [M]+. – C7H5FN2O2 (168.13):
calcd. C 50.01, H 3.00, N 16.66; found C 49.79, H 2.85,
N 16.45.
5-Nitro-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione (2e)
Pale-yellow powder; m. p. 197 – 199 ◦C; yield: 1.46 g
(75 %). – IR (KBr): ν = 1672 (C=O), 3369 cm−1 (NH). –
1H NMR ([D6]DMSO): δ = 3.22 (s, 1H, HC≡C-), 3.97 (s,
Experimental Section
All solvents were dried by standard methods. Melting 2H, NCH2), 9.80 (s, 1H, 6-H), 9.90 (brs, 1H, NH). – MS (EI,
points were determined with a Kofler block apparatus and are 70 eV): m/z (%) = 195 (63) [M]+. – C7H5N3O4 (195.13):
uncorrected. IR spectra were recorded with a Perkin-Elmer calcd. C 43.09, H 2.58, N 21.53; found C 42.88, H 2.41,
Model 1720 FTIR spectrometer. Specific rotations are given N 21.34.
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5-Methoxymethyl-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-
Ethyl 5-{(1S,2R,3R)-4-{4-[(2,4-dioxo-3,4-dihydropyrimidin-
dione (2f)
1(2H)yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-trihydroxy-
butyl}furan-3-carboxylate (4a)
Colorless powder; m. p. 155 – 157 ◦C; yield: 1.53 g
(79 %). – IR (KBr): ν = 1667 (C=O), 3365 cm−1 (NH). –
1H NMR ([D6]DMSO): δ = 3.16 (s, 1H, HC≡C-), 3.39 (s,
3H, OCH3), 3.99 (s, 2H, NCH2), 4.12 (s, 2H, OCH2), 7.89 (s,
1H, 6-H), 9.88 (brs, 1H, NH). – 13C NMR ([D6]DMSO): δ =
35.72 (CH2), 58.24 (OCH3), 63.28 (CH2), 76.89 (HC≡C),
81.80 (HC≡C), 111.18 (C-5), 148.58 (C-2), 153.68 (C-6),
160.88 (C-4). – MS (EI, 70 eV): m/z (%) = 194 (73) [M]+. –
C9H10N2O3 (194.19): calcd. C 55.67, H 5.19, N 14.43;
found C 55.51, H 5.13, N 14.37.
Colorless powder; m. p. 260 – 262 ◦C; yield: 3.87 g
(89 %). – [α]D: +40. – IR (KBr): ν = 1669 (C=O),
1735 (C=O), 3358 (NH), 3475 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 1.30 (t, 3H, J = 5.2 Hz, CH3CH2), 3.30
(m, 1H, CH), 3.58 (brs, 3H, 3 OH), 3.71 (m, 1H, CH), 3.79,
4.00 (2d, 2H, J = 4.0 Hz, NCH2), 4.32 (q, 2H, J = 5.2 Hz,
CH3CH2), 4.51 (s, 2H, NCH2), 4.83 (m, 1H, CH), 5.79 (d,
1H, J = 6.5 Hz, 5-H), 6.75 (s, 1H, 4-H furan), 7.65 (s, 1H,
5-H triazole), 7.83 (s, 1H, 2-H furan), 9.66 (d, 1H, J = 6.5 Hz,
6-H), 9.92 (brs, 1H, NH). – 13C NMR ([D6]DMSO): δ =
15.20 (CH3), 47.75, 52.84 (2 NCH2), 60.42 (CH2), 62.15
(OCH2), 74.24, 75.12, 76.18 (3 CH), 104.22, 112.52, 116.68,
120.37, 123.24, 127.59, 136.71, 147.29, 150.18, 154.41,
155.36 (Ar-C, C-2, C-5, C-6), 160.14 (C-4), 164.24 (C=O). –
MS (EI, 70 eV): m/z (%) = 435 (43) [M]+. – C18H21N5O8
(435.39): calcd. C 49.66, H 4.86, N 16.09; found C 49.45,
H 4.65, N 15.88.
5-Pentyloxymethyl-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-
dione (2g)
Colorless powder; m. p. 148 – 150 ◦C; yield: 2.07 g
(83 %). – IR (KBr): ν = 1670 (C=O), 3368 cm−1 (NH). –
1H NMR ([D6]DMSO): δ = 0.94 (t, 3H, J = 5.5 Hz, CH3),
1.33 – 1.55 (m, 6H, 3CH2), 3.16 (s, 1H, HC≡C-), 3.36 (t, 2H,
J = 5.6 Hz, OCH2), 3.92 (s, 2H, NCH2), 4.16 (s, 2H, OCH2),
7.83 (s, 1H, 6-H), 9.79 (brs, 1H, NH). – MS (EI, 70 eV):
m/z (%) = 250 (80) [M]+. – C13H18N2O3 (250.29): calcd.
C 62.38, H 7.25, N 11.19; found C 62.23, H 7.12, N 11.07.
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-methyl-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carboxylate (4b)
Colorless powder; m. p. 231 – 233 ◦C; yield: 4.19 g
(92 %). – [α]D: +6.9. – IR (KBr): ν = 1667 (C=O),
1738 (C=O), 3360 (NH), 3477 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 1.23 (t, 3H, J = 5.2 Hz, CH3CH2), 2.45
(s, 3H, CH3), 3.27 (m, 1H, CH), 3.58 (brs, 3H, 3 OH), 3.71
(m, 1H, CH), 3.83, 4.03 (2d, 2H, J = 4.0 Hz, NCH2), 4.29 (q,
2H, J = 5.2 Hz, CH3CH2), 4.56 (s, 2H, NCH2), 4.78 (m, 1H,
CH), 6.83 (s, 1H, 4-H furan), 7.63 (s, 1H, 6-H), 7.67 (s, 1H,
5-H triazole), 7.79 (s, 1H, 2-H furan), 9.98 (brs, 1H, NH). –
13C NMR ([D6]DMSO): δ = 14.88 (CH3), 15.24 (CH3),
47.71, 53.28 (2 NCH2), 60.45 (CH2), 62.32 (OCH2), 74.21,
75.32, 76.20 (3 CH), 104.31, 112.55, 116.49, 120.35, 123.24,
127.51, 136.70, 147.33, 150.52, 154.92, 155.80 (Ar-C, C-2,
C-5, C-6), 160.35 (C-4), 164.25 (C=O). – MS (EI, 70 eV):
m/z (%) = 449 (32) [M]+. – C19H23N5O8 (449.41): calcd.
C 50.78, H 5.16, N 15.58; found C 50.59, H 5.03, N 15.43.
5-Benzyloxymethyl-1-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-
dione (2h)
Colorless powder; m. p. 181 – 183 ◦C; yield: 2.29 g
(85 %). – IR (KBr): ν = 1675 (C=O), 3359 cm−1 (NH). –
1H NMR ([D6]DMSO): δ = 3.12 (s, 1H, HC≡C-), 3.98 (s,
2H, NCH2), 4.13 (s, 2H, OCH2), 4.86 (s, 2H, OCH2), 7.33 –
7.48 (m, 5H, Ar-H), 7.79 (s, 1H, 6-H), 9.82 (brs, 1H, NH). –
13C NMR ([D6]DMSO): δ = 35.85 (CH2), 61.10, 61.28
(2 CH2), 76.85 (HC≡C), 81.82 (HC≡C), 111.21 (C-5),
116.60, 120.37, 127.56, 151.15, 153.46, 155.07 (Ar-C, C-2,
C-6), 160.82 (C-4). – MS (EI, 70 eV): m/z (%) = 270 (80)
[M]+. – C15H14N2O3 (270.28): calcd. C 66.66, H 5.22,
N 10.36; found C 66.51, H 5.18, N 10.21.
General procedure for the synthesis of 5-substituted ethyl
5-{(1S,2R,3R)-4-{4-[(2,4-dioxo-3,4-dihydropyrimidin-
1(2H)yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-trihydroxy-
butyl}furan-3-carboxylates 4a – h
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-bromo-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carboxylate (4c)
A solution of an alkyne 2a – h (5 mmol), the respective
Yellow powder; m. p. 288 – 290 ◦C; yield: 4.52 g (88 %). –
azide 3 (4 mmol), 2,6-lutidine (5 mmol), and CuI (0.4 mmol) [α]D: +0.3. – IR (KBr): ν = 1668 (C=O), 1737 (C=O), 3364
in tBuOH (10 mL) was stirred for 10 – 12 h at 0 ◦C. The sol- (NH), 3472 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 1.27
vent was evaporated under reduced pressure, and the residue (t, 3H, J = 5.2 Hz, CH3CH2), 3.33 (m, 1H, CH), 3.58 (brs,
was purified by silica gel column chromatography using 3H, 3 OH), 3.70 (m, 1H, CH), 3.75, 4.03 (2d, 2H, J = 4.0 Hz,
0.3 % MeOH in CH2Cl2 to afford the corresponding 1,2,3- NCH2), 4.38 (q, 2H, J = 5.2 Hz, CH3CH2), 4.49 (s, 2H,
triazole derivatives 4a – h.
NCH2), 4.80 (m, 1H, CH), 6.78 (s, 1H, 4-H furan), 7.59 (s,
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
1H, 5-H triazole), 7.80 (s, 1H, 2-H furan), 8.11 (s, 1H, 6-H), CH), 6.74 (s, 1H, 4-H furan), 7.68 (s, 1H, 5-H triazole), 7.70
9.88 (brs, 1H, NH). – MS (EI, 70 eV): m/z (%) = 513/515 (22) (s, 1H, 6-H), 7.87 (s, 1H, 2-H furan), 9.80 (brs, 1H, NH). –
[M]+. – C18H20BrN5O8 (514.28): calcd. C 42.04, H 3.92, MS (EI, 70 eV): m/z (%) = 479 (12) [M]+. – C20H25N5O9
N 13.62; found C 41.89, H 3.83, N 13.56.
(479.44): calcd. C 50.10, H 5.26, N 14.61; found C 50.03,
H 5.13, N 14.55.
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-flouro-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carboxylate (4d)
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-pentoxymethyl-2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-
1,2,3-trihydroxybutyl}furan-3-carboxylate (4g)
Colorless powder; m. p. 270 – 272 ◦C; yield: 3.94 g
(87 %). – [α]D: +13. – IR (KBr): ν = 1668 (C=O),
1735 (C=O), 3363 (NH), 3477 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 1.33 (t, 3H, J = 5.2 Hz, CH3CH2), 3.27
(m, 1H, CH), 3.54 (brs, 3H, 3 OH), 3.66 (m, 1H, CH), 3.81,
4.07 (2d, 2H, J = 4.0 Hz, NCH2), 4.36 (q, 2H, J = 5.2 Hz,
CH3CH2), 4.48 (s, 2H, NCH2), 4.87 (m, 1H, CH), 6.70 (s,
1H, 4-H furan), 7.71 (s, 1H, H-5 triazole), 7.87 (s, 1H, 2-H
furan), 8.05 (s, 1H, 6-H), 9.81 (brs, 1H, NH). – 13C NMR
([D6]DMSO): δ = 15.22 (CH3), 47.68, 53.50 (2 NCH2),
60.51 (CH2), 62.18 (OCH2), 74.33, 75.94, 76.87 (3 CH),
104.30, 112.52, 116.65, 120.40, 123.24, 127.62, 136.83,
147.48, 150.19, 154.41, 155.31 (Ar-C, C-2, C-5, C-6),
159.18 (C-4), 164.24 (C=O). – MS (EI, 70 eV): m/z (%) =
453 (28) [M]+. – C18H20FN5O8 (453.38): calcd. C 47.68,
H 4.45, N 15.45; found C 47.51, H 4.29, N 15.31. Ethyl
Colorless powder; m. p. 215 – 217 ◦C; yield: 4.92 g
(92 %). – [α]D: +21. – IR (KBr): ν = 1668 (C=O),
1740 (C=O), 3368 (NH), 3474 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 0.90 (t, 3H, J = 5.5 Hz, CH3), 1.23 – 1.50
(m, 8H, 3CH2, CH3CH2), 3.30 – 3.40 (m, 3H, CH, OCH2),
3.58 (brs, 3H, 3 OH), 3.77 (m, 1H, CH), 3.78 – 4.09 (m, 4H,
NCH2, OCH2), 4.39 (q, 2H, J = 5.2 Hz, CH3CH2), 4.47 (s,
2H, NCH2), 4.88 (m, 1H, CH), 6.71 (s, 1H, H-4 furan), 7.60
(s, 1H, 5-H triazole), 7.71 (s, 1H, 6-H), 7.86 (s, 1H, 2-H fu-
ran), 9.90 (brs, 1H, NH). – MS (EI, 70 eV): m/z (%) = 535
(11) [M]+. – C24H33N5O9 (535.55): calcd. C 53.82, H 6.21,
N 13.08; found C 53.67, H 6.11, N 13.01.
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-benzyloxymethyl-2,4-dioxo-
3,4-dihydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-
yl}-1,2,3-trihydroxybutyl}furan-3-carboxylate (4h)
Colorless powder; m. p. 227 – 229 ◦C; yield: 5.21 g
(94 %). – [α]D: +34.1. – IR (KBr): ν = 1670 (C=O),
1741 (C=O), 3368 (NH), 3479 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 1.27 (t, 3H, J = 5.2 Hz, CH3CH2), 3.30
(m, 1H, CH), 3.57 (brs, 3H, 3 OH), 3.70 (m, 1H, CH),
3.80 – 4.09 (m, 4H, NCH2, OCH2), 4.37 (q, 2H, J = 5.2 Hz,
CH3CH2), 4.58 (s, 2H, NCH2), 4.79 – 4.85 (m, 3H, CH,
OCH2), 6.73 (s, 1H, 4-H furan), 7.38 – 7.50 (m, 5H, Ar-H),
7.64 (s, 1H, 5-H triazole), 7.73 (s, 1H, 6-H), 7.80 (s, 1H,
2-H furan), 9.81 (brs, 1H, NH). – 13C NMR ([D6]DMSO):
δ = 15.27 (CH3), 46.95, 53.32 (2 NCH2), 60.12, 60.24, 61.38
(3 CH2), 74.39, 75.18, 76.77 (3 CH), 102.21, 104.48, 120.59,
124.53, 136.76, 146.37, 150.24, 151.87, 155.43 (Ar-C, C-2,
C-5, C-6), 160.05 (C-4), 164.21 (C=O). – MS (EI, 70 eV):
m/z (%) = 555 (17) [M]+. – C26H29N5O9 (555.54): calcd.
C 56.21, H 5.26, N 12.61; found C 56.11, H 5.12, N 12.44.
5-{(1S,2R,3R)-4-{4-[(5-nitro-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carboxylate (4e)
Pale-yellow powder; m. p. 266 – 268 ◦C; yield: 4.08 g
(85 %). – [α]D: +12.7. – IR (KBr): ν = 1672 (C=O),
1740 (C=O), 3368 (NH), 3479 cm−1 (OH). – 1H NMR
([D6]DMSO): δ = 1.23 (t, 3H, J = 5.2 Hz, CH3CH2), 3.25
(m, 1H, CH), 3.49 (brs, 3H, 3 OH), 3.66 (m, 1H, CH), 3.70,
3.98 (2d, 2H, J = 4.0 Hz, NCH2), 4.39 (q, 2H, J = 5.2 Hz,
CH3CH2), 4.56 (s, 2H, NCH2), 4.87 (m, 1H, CH), 6.71 (s,
1H, 4-H furan), 7.60 (s, 1H, 5-H triazole), 7.85 (s, 1H, 2-H
furan), 9.80 (s, 1H, 6-H), 9.99 (brs, 1H, NH). – MS (EI,
70 eV): m/z (%) = 480 (32) [M]+. – C18H20N6O10 (480.39):
calcd. C 45.00, H 4.20, N 17.49; found C 44.81, H 4.07,
N 17.36.
Ethyl 5-{(1S,2R,3R)-4-{4-[(5-methoxymethyl-2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-
1,2,3-trihydroxybutyl}furan-3-carboxylate (4f)
General procedure for the synthesis of 5-substituted
5-{(1S,2R,3R)-4-{4-[(2,4-dioxo-3,4-dihydropyrimidin-
1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-trihydroxy-
butyl}furan-3-carbohydrazides 5a – h
Colorless powder; m. p. 239 – 241 ◦C; yield: 4.45 g
(93 %). – [α]D: +43. – IR (KBr): ν = 1669 (C=O),
To a solution of an ethyl ester 4a – h (10 mmol) in EtOH
1739 (C=O), 3368 (NH), 3475 cm−1 (OH). – 1H NMR (15 mL) was added hydrazine hydrate (0.5 g, 10 mmol), and
([D6]DMSO): δ = 1.28 (t, 3H, J = 5.2 Hz, CH3CH2), 3.25 the reaction mixture was heated under reflux for 4 – 5 h. The
(m, 1H, CH), 3.40 (s, 3H, OCH3), 3.56 (brs, 3H, 3 OH), 3.78 volume of the solvent was reduced under vacuum, and the
(m, 1H, CH), 3.70 – 4.08 (m, 4H, NCH2, OCH2), 4.44 (q, precipitated solid was filtered, washed with cold ethanol and
2H, J = 5.2 Hz, CH3CH2), 4.50 (s, 2H, NCH2), 4.80 (m, 1H, recrystallized from ethanol to afford the hydrazides 5a – h.
Unauthenticated
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
63
5-{(1S,2R,3R)-4-{4-[(2,4-Dioxo-3,4-dihydropyrimidin-
1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-trihydroxy-
butyl}furan-3-carbohydrazide (5a)
(NH), 3473 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.29
(m, 1H, CH), 3.52 (brs, 3H, 3 OH), 3.63 (m, 1H, CH), 3.82,
4.11 (2d, 2H, J = 4.0 Hz, NCH2), 4.49 (s, 2H, NCH2), 4.92
(m, 1H, CH), 5.82 (brs, 2H, NH2), 6.74 (s, 1H, 4-H furan),
7.75 (s, 1H, 5-H triazole), 7.88 (s, 1H, 2-H furan), 8.04 (s,
1H, 6-H), 8.96 (brs, 1H, NH), 9.80 (brs, 1H, NH). – MS (EI,
70 eV): m/z (%) = 440 (22) [M+1]+.
◦
Colorless powder; m. p. 312 – 314 C; yield: 3.91 g (90
%). – [α]D: +21. – IR (KBr): ν = 1680 (C=O), 3367 (NH),
3480 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.32 (m,
1H, CH), 3.57 (brs, 3H, 3 OH), 3.75 (m, 1H, CH), 3.82, 4.02
(2d, 2H, J = 4.0 Hz, NCH2), 4.50 (s, 2H, NCH2), 4.85 (m,
1H, CH), 5.76 (brs, 2H, NH2), 5.81 (d, 1H, J = 6.5 Hz, 5-H),
6.77 (s, 1H, 4-H furan), 7.67 (s, 1H, 5-H triazole), 7.85 (s,
1H, 2-H furan), 8.98 (brs, 1H, NH), 9.68 (d, 1H, J = 6.5 Hz,
6-H), 9.91 (brs, 1H, NH). – 13C NMR ([D6]DMSO): δ =
47.82, 52.29 (2 NCH2), 74.29, 75.15, 77.10 (3 CH), 103.28,
104.37, 121.82, 123.27, 127.71, 136.70, 137.66, 147.25,
151.19, 155.42 (Ar-C, C-2, C-5, C-6), 160.18 (C-4), 165.20
(C=O). – MS (EI, 70 eV): m/z (%) = 422 (35) [M+1]+.
5-{(1S,2R,3R)-4-{4-[(5-Nitro-2,4-dioxo-3,4-dihydropyr-
imidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carbohydrazide (5e)
Colorless powder; m. p. 273 – 275 ◦C; yield: 4.08 g
(85 %). – [α]D: +10. – IR (KBr): ν = 1681 (C=O), 3370
(NH), 3478 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.28
(m, 1H, CH), 3.48 (brs, 3H, 3 OH), 3.64 (m, 1H, CH), 3.73,
4.05 (2d, 2H, J = 4.0 Hz, NCH2), 4.58 (s, 2H, NCH2), 4.86
(m, 1H, CH), 5.80 (brs, 2H, NH2), 6.70 (s, 1H, 4-H furan),
7.62 (s, 1H, 5-H triazole), 7.88 (s, 1H, 2-H furan), 9.11 (brs,
1H, NH), 9.89 (s, 1H, 6-H), 10.02 (brs, 1H, NH). – MS (EI,
70 eV): m/z (%) = 467 (32) [M+1]+.
5-{(1S,2R,3R)-4-{4-[(5-Methyl-2,4-dioxo-3,4-dihydropyr-
imidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-tri-
hydroxybutyl}furan-3-carbohydrazide (5b)
Colorless powder; m. p. 280 – 282 ◦C; yield: 4.09 g
(91 %). – [α]D: +7.8. – IR (KBr): ν = 1678 (C=O), 3370
(NH), 3475 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 2.32
(s, 3H, CH3), 3.29 (m, 1H, CH), 3.56 (brs, 3H, 3 OH), 3.72
(m, 1H, CH), 3.82, 4.05 (2d, 2H, J = 4.0 Hz, NCH2), 4.59 (s,
2H, NCH2), 4.80 (m, 1H, CH), 5.77 (brs, 2H, NH2), 6.85 (s,
1H, 4-H furan), 7.66 (s, 1H, 6-H), 7.69 (s, 1H, 5-H triazole),
7.84 (s, 1H, 2-H furan), 8.96 (brs, 1H, NH), 9.94 (brs, 1H,
NH). – MS (EI, 70 eV): m/z (%) = 436 (24) [M+1]+.
5-{(1S,2R,3R)-4-{4-[(5-Methoxymethyl-2,4-dioxo-3,4-di-
hydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-
1,2,3-trihydroxybutyl}furan-3-carbohydrazide (5f)
Colorless powder; m. p. 267 – 269 ◦C; yield: 4.16 g
(87 %). – [α]D: +37. – IR (KBr): ν = 1680 (C=O), 3368
(NH), 3480 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.24
(m, 1H, CH), 3.42 (s, 3H, OCH3), 3.55 (brs, 3H, 3 OH),
3.78 (m, 1H, CH), 3.72 – 4.11 (m, 4H, NCH2, OCH2), 4.48
(s, 2H, NCH2), 4.78 (m, 1H, CH), 5.78 (brs, 2H, NH2),
6.70 (s, 1H, 4-H furan), 7.69 (s, 1H, 5-H triazole), 7.71 (s,
1H, 6-H), 7.86 (s, 1H, 2-H furan), 9.05 (brs, 1H, NH), 9.85
(brs, 1H, NH). – 13C NMR ([D6]DMSO): δ = 47.68, 53.75
(2 NCH2), 57.35 (OCH3), 63.32 (OCH2), 74.25, 75.16, 76.24
(3 CH), 106.26, 112.20, 121.39, 123.26, 136.75, 137.69,
145.21, 151.20, 155.31 (Ar-C, C-2, C-5, C-6), 160.14 (C-4),
166.20 (C=O) pm. – MS (EI, 70 eV): m/z (%) = 466 (18)
[M+1]+.
5-{(1S,2R,3R)-4-{4-[(5-Bromo-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carbohydrazide (5c)
Colorless powder; m. p. 322 – 324 ◦C; yield: 4.57 g
(89 %). – [α]D: +0.1. – IR (KBr): ν = 1682 (C=O), 3368
(NH), 3477 cm−1 (OH). – 1H NMR ([D6]DMSO): δ =
3.34 (m, 1H, CH), 3.58 (brs, 3H, 3 OH), 3.71 (m, 1H,
CH), 3.77, 4.04 (2d, 2H, J = 4.0 Hz, NCH2), 4.50 (s, 2H,
NCH2), 4.82 (m, 1H, CH), 5.84 (brs, 2H, NH2), 6.77 (s, 1H,
4-H furan), 7.70 (s, 1H, 5-H triazole), 7.84 (s, 1H, 2-H fu-
ran), 8.14 (s, 1H, 6-H), 9.02 (brs, 1H, NH), 9.90 (brs, 1H,
NH). – 13C NMR ([D6]DMSO): δ = 47.74, 53.87 (2 NCH2),
74.27, 75.14, 76.21 (3 CH), 103.26, 106.15, 121.40, 123.37,
136.72, 137.69, 145.31, 151.23, 154.38 (Ar-C, C-2, C-5,
C-6), 157.20 (C-4), 165.29 (C=O). – MS (EI, 70 eV): m/z
(%) = 500/502 (16) [M+1]+.
5-{(1S,2R,3R)-4-{4-[(5-Pentoxymethyl-2,4-dioxo-3,4-di-
hydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-
1,2,3-trihydroxybutyl}furan-3-carbohydrazide (5g)
Colorless powder; m. p. 239 – 241 ◦C; yield: 4.62 g
(84 %). – [α]D: +17. – IR (KBr): ν = 1676 (C=O), 3362
(NH), 3478 cm−1 (OH). – 1H NMR ([D6]DMSO): δ =
1.22 – 1.50 (m, 9H, 3CH2, CH3CH2), 3.31 – 3.42 (m, 3H,
CH, OCH2), 3.58 (brs, 3H, 3 OH), 3.74 (m, 1H, CH), 3.78 –
4.10 (m, 4H, NCH2, OCH2), 4.48 (s, 2H, NCH2), 4.86 (m,
1H, CH), 5.80 (brs, 2H, NH2), 6.77 (s, 1H, 4-H furan),
5-{(1S,2R,3R)-4-{4-[(5-Fluoro-2,4-dioxo-3,4-dihydro-
pyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-yl}-1,2,3-
trihydroxybutyl}furan-3-carbohydrazide (5d)
Colorless powder; m. p. 293 – 295 ◦C; yield: 4.08 g 7.72 (s, 1H, 5-H triazole), 7.78 (s, 1H, 6-H), 7.88 (s, 1H,
(90 %). – [α]D: +17. – IR (KBr): ν = 1677 (C=O), 3369 2-H furan), 9.02 (brs, 1H, NH), 9.94 (brs, 1H, NH). – 13C
Unauthenticated
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64
W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
NMR ([D6]DMSO): δ = 16.24 (CH3), 26.18, 31.88, 36.15 53.18 (2 NCH2), 74.47, 75.28, 76.20 (3 CH), 102.25, 104.31,
(3 CH2), 47.71, 53.77 (2 NCH2), 63.42, 67.62 (2 OCH2), 112.30, 123.98, 136.70, 142.28, 148.12, 151.19, 152.67,
74.28, 75.18, 76.25 (3 CH), 106.26, 112.22, 121.42, 123.26, 154.38 (Ar-C, C-2, C-5, C-6), 160.14 (C-4), 172.24 (C=S). –
136.77, 137.70, 145.24, 151.21, 155.42 (Ar-C, C-2, C-5, MS (EI, 70 eV): m/z (%) = 463 (15) [M]+. – C17H17N7O7S
C-6), 160.18 (C-4), 166.21 (C=O) pm. – MS (EI, 70 eV): (463.42): calcd. C 44.06, H 3.70, N 21.16; found C 43.89,
m/z ( %) = 522 (21) [M+1]+.
H 3.57, N 21.07.
5-{(1S,2R,3R)-4-{4-[(5-Benzyloxymethyl-2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)methyl]-1H-1,2,3-triazol-1-
yl}-1,2,3-trihydroxybutyl}furan-3-carbohydrazide (5h)
5-Methyl-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-dihydro-
1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-trihydroxybutyl}-
1H-1,2,3-triazol-4-yl}methyl}pyrimidine-2,4(1H,3H)-
dione (6b)
Colorless powder; m. p. 241 – 243 ◦C; yield: 4.65 g
(86 %). – [α]D: +29. – IR (KBr): ν = 1677 (C=O), 3365
Pale-yellow powder; m. p. 305 – 307 ◦C; yield: 4.24 g
(NH), 3477 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.28 (89 %). – [α]D: +5.2. – IR (KBr): ν = 1668 (C=O), 3364
(m, 1H, CH), 3.54 (brs, 3H, 3 OH), 3.67 (m, 1H, CH), 3.77 – (NH), 3478 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 2.45
4.08 (m, 4H, NCH2, OCH2), 4.55 (s, 2H, NCH2), 4.60 – (s, 1H, CH3), 3.28 (m, 1H, CH), 3.66 (brs, 3H, 3 OH),
4.87 (m, 3H, CH, OCH2), 5.76 (brs, 2H, NH2), 6.71 (s, 1H, 3.70 (m, 1H, CH), 3.78, 4.00 (2d, 2H, J = 4.0 Hz, NCH2),
4-H furan), 7.36 – 7.47 (m, 5H, Ar-H), 7.62 (s, 1H, 5-H tria- 4.53 (s, 2H, NCH2), 4.88 (m, 1H, CH), 6.48 (s, 1H, 4-H
zole), 7.70 (s, 1H, 6-H), 7.79 (s, 1H, 2-H furan), 8.97 (brs, furan), 7.60 (s, 1H, 5-H triazole), 7.68 (s, 2H, 2-H furan,
1H, NH), 9.80 (brs, 1H, NH). – 13C NMR ([D6]DMSO): 6-H), 10.03 (brs, 1H, NH), 13.00 (brs, 1H, NH). – 13C NMR
δ = 47.28, 53.98 (2 NCH2), 68.05, 68.37 (2 OCH2), 74.28, ([D6]DMSO): δ = 15.12 (CH3), 47.72, 53.28 (2 NCH2),
75.19, 77.10 (3 CH), 106.28, 121.39, 123.24, 126.68, 127.39, 74.28, 76.12, 77.14 (3 CH), 102.21, 108.23, 112.42, 123.78,
129.70, 131.16, 132.46, 136.40, 137.63, 139.11, 151.19, 136.70, 141.24, 145.27, 151.31, 152.49, 154.52 (Ar-C, C-2,
155.41 (Ar-C, C-2, C-5, C-6), 160.18 (C-4), 164.28 (C=O). – C-5, C-6), 160.18 (C-4), 172.34 (C=S). – MS (EI, 70 eV):
MS (EI, 70 eV): m/z (%) = 542 (15) [M+1]+.
m/z (%) = 477 (23) [M]+. – C18H19N7O7S (477.45): calcd.
C 45.28, H 4.01, N 20.54; found C 45.14, H 3.88, N 20.33.
General procedure for the synthesis of 5-substituted
1-{1-{(2R,3R,4S)-4-[4-(5-mercapto-1,3,4-oxadiazol-2-
yl)furan-2-yl]-2,3,4-trihydroxybutyl}-1H-1,2,3-triazol-4-
yl}methyl}pyrimidine-2,4(1H,3H)-diones 6a – h
5-Bromo-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-dihydro-
1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-trihydroxybutyl}-
1H-1,2,3-triazol-4-yl}methyl}pyrimidine-2,4(1H,3H)-
dione (6c)
A mixture of a hydrazide 5a – h (10 mmol) and carbon
disulfide (0.6 mL, 10 mmol) was added to a solution of
Yellow powder; m. p. 341 – 343 ◦C; yield: 4.87 g (90 %). –
KOH (0.56 g, 10 mmol) in a mixture of water and ethanol [α]D: +0.7. – IR (KBr): ν = 1667 (C=O), 3365 (NH),
(1 : 4) (50 mL). The reaction mixture was refluxed for 4 h. 3479 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.26 (m,
After evaporation under reduced pressure, a solid was ob- 1H, CH), 3.61 (brs, 3H, 3 OH), 3.69 (m, 1H, CH), 3.77, 4.00
tained, which was dissolved in water (50 mL) and acidified (2d, 2H, J = 4.0 Hz, NCH2), 4.51 (s, 2H, NCH2), 4.75 (m,
with conc. HCl. The precipitate was filtered off, washed with 1H, CH), 6.45 (s, 1H, 4-H furan), 7.60 (s, 1H, 5-H triazole),
H2O, and recrystallized from ethanol to afford the corre- 7.70 (s, 1H, 2-H furan), 8.08 (s, 1H, 6-H), 9.90 (brs, 1H, NH),
sponding 1,3,4-oxadiazoles 6a – h.
12.93 (brs, 1H, NH). – MS (EI, 70 eV): m/z (%) = 541/543
(17) [M]+. – C17H16BrN7O7S (542.32): calcd. C 37.65,
H 2.97, N 18.08; found C 37.51, H 2.78, N 17.79.
1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-dihydro-1,3,4-oxa-
diazol-2-yl)furan-2-yl]-2,3,4-trihydroxybutyl}-1H-1,2,3-
triazol-4-yl}methyl}pyrimidine-2,4(1H,3H)-dione (6a)
5-Fluoro-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-dihydro-
1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-trihydroxybutyl}-
1H-1,2,3-triazol-4-yl}methyl}pyrimidine-2,4(1H,3H)-
dione (6d)
Pale-yellow powder; m. p. 333 – 335 ◦C; yield: 4.07 g
(88 %). – [α]D: +26.7. – IR (KBr): ν = 1669 (C=O), 3360
(NH), 3479 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.33
(m, 1H, CH), 3.60 (brs, 3H, 3 OH), 3.75 (m, 1H, CH), 3.71,
Pale-yellow powder; m. p. 315 – 317 ◦C; yield: 3.84 g
4.02 (2d, 2H, J = 4.0 Hz, NCH2), 4.48 (s, 2H, NCH2), 4.80 (80 %). – [α]D: +23. – IR (KBr): ν = 1670 (C=O), 3368
(m, 1H, CH), 5.77 (d, 1H, J = 6.5 Hz, 5-H), 6.55 (s, 1H, (NH), 3477 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.30
4-H furan), 7.64 (s, 1H, 5-H triazole), 7.73 (s, 1H, 2-H fu- (m, 1H, CH), 3.55 (brs, 3H, 3 OH), 3.69 (m, 1H, CH), 3.76,
ran), 8.55 (d, 1H, J = 6.5 Hz, 6-H), 10.00 (brs, 1H, NH), 4.00 (2d, 2H, J = 4.0 Hz, NCH2), 4.49 (s, 2H, NCH2), 4.85
13.05 (brs, 1H, NH). – 13C NMR ([D6]DMSO): δ = 47.92, (m, 1H, CH), 6.59 (s, 1H, 4-H furan), 7.68 (s, 1H, 5-H tri-
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W. A. El-Sayed – A. A.-H. Abdel-Rahman · Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles
65
azole), 7.78 (s, 1H, 2-H furan), 8.00 (s, 1H, 6-H), 9.88 (brs, 74.25, 75.14, 76.86 (3 CH), 101.24, 112.14, 114.38, 124.18,
1H, NH), 13.02 (brs, 1H, NH). – MS (EI, 70 eV): m/z ( %) = 137.24, 142.20, 147.25, 151.10, 152.70, 154.82 (Ar-C, C-2,
481 (23) [M]+. – C17H16FN7O7S (481.42): calcd. C 42.41, C-5, C-6), 159.84 (C-4), 172.22 (C=S). – MS (EI, 70 eV):
H 3.35, N 20.37; found C 42.33, H 3.23, N 20.11.
m/z (%) = 507 (25) [M]+. – C19H21N7O8S (507.48):
calcd. C 44.97, H 4.17, N 19.32; found C 44.83, H 4.09,
N 19.12.
5-Nitro-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-dihydro-
1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-trihydroxybutyl}-
1H-1,2,3-triazol-4-yl}methyl}pyrimidine-2,4(1H,3H)-
dione (6e)
5-Pentoxymethyl-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-4,5-
dihydro-1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-trihydr-
oxybutyl}-1H-1,2,3-triazol-4-yl}methyl}pyrimidine-
2,4(1H,3H)-dione (6g)
Yellow powder; m. p. 294 – 296 ◦C; yield: 4.06 g (80 %). –
[α]D: +20.1. – IR (KBr): ν = 1667 (C=O), 3364 (NH),
3480 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.27 (m,
1H, CH), 3.63 (brs, 3H, 3 OH), 3.69 (m, 1H, CH), 3.77, 4.01
(2d, 2H, J = 4.0 Hz, NCH2), 4.53 (s, 2H, NCH2), 4.77 (m,
1H, CH), 6.53 (s, 1H, 4-H furan), 7.59 (s, 1H, 5-H triazole),
7.69 (s, 1H, 2-H furan), 8.85 (s, 1H, 6-H), 9.94 (brs, 1H, NH),
13.00 (brs, 1H, NH). – 13C NMR ([D6]DMSO): δ = 48.12,
53.24 (2 NCH2), 74.32, 75.15, 76.30 (3 CH), 103.34, 114.32,
123.28, 130.89, 137.22, 142.25, 147.28, 152.19, 153.48,
154.12, 155.46 (Ar-C, C-2, C-4, C-5, C-6), 172.42 (C=S). –
MS (EI, 70 eV): m/z (%) = 508 (17) [M]+. – C17H16N8O9S
(508.42): calcd. C 40.16, H 3.17, N 22.04; found C 40.00,
H 3.05, N 21.88.
Pale-yellow powder; m. p. 266 – 268 ◦C; yield: 5.01 g
(89 %). – [α]D: +36.2. – IR (KBr): ν = 1670 (C=O), 3369
(NH), 3479 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 0.91
(t, 3H, J = 5.5 Hz, CH3), 1.29 – 1.48 (m, 6H, 3CH2), 3.30 –
3.38 (m, 3H, CH, OCH2), 3.58 (brs, 3H, 3 OH), 3.69 (m,
1H, CH), 3.75 – 4.05 (m, 4H, NCH2, OCH2), 4.54 (s, 2H,
NCH2), 4.84 (m, 1H, CH), 6.55 (s, 1H, 4-H furan), 7.60 (s,
1H, 5-H triazole), 7.77 (s, 2H, 2-H furan, 6-H), 10.02 (brs,
1H, NH), 13.06 (brs, 1H, NH). – MS (EI, 70 eV): m/z (%) =
563 (19) [M]+. – C23H29N7O8S (563.58): calcd. C 49.02,
H 5.19, N 17.40; found C 48.82, H 5.00, N 17.27.
5-Benzyloxymethyl-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-
4,5-dihydro-1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-tri-
hydroxybutyl}-1H-1,2,3-triazol-4-yl}methyl}pyrimidine-
2,4(1H,3H)-dione (6h)
5-Methoxymethyl-1-{{1-{(2R,3R,4S)-4-[4-(5-thioxo-
4,5-dihydro-1,3,4-oxadiazol-2-yl)furan-2-yl]-2,3,4-tri-
hydroxybutyl}-1H-1,2,3-triazol-4-yl}methyl}pyrimidine-
2,4(1H,3H)-dione (6f)
Pale-yellow powder; m. p. 277 – 279 ◦C; yield: 5.30 g
Pale-yellow powder; m. p. 280 – 282 ◦C; yield: 4.25 g (91 %). – [α]D: +25.8. – IR (KBr): ν = 1671 (C=O), 3365
(84 %). – [α]D: +29.7. – IR (KBr): ν = 1669 (C=O), 3368 (NH), 3476 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.30
(NH), 3477 cm−1 (OH). – 1H NMR ([D6]DMSO): δ = 3.28 – (m, 1H, CH), 3.63 (brs, 3H, 3 OH), 3.73 (m, 1H, CH), 3.76 –
3.37 (m, 3H, CH, OCH3), 3.62 (brs, 3H, 3 OH), 3.73 (m, 4.04 (m, 4H, NCH2, OCH2), 4.49 (s, 2H, NCH2), 4.77 (m,
1H, CH), 3.71 – 4.02 (m, 4H, NCH2, OCH2), 4.53 (s, 2H, 1H, CH), 6.57 (s, 1H, 4-H furan), 7.69 (s, 1H, 5-H triazole),
NCH2), 4.85 (m, 1H, CH), 6.54 (s, 1H, 4-H furan), 7.60 (s, 7.77 (s, 2H, 2-H furan, 6-H), 10.00 (brs, 1H, NH), 13.00 (brs,
1H, 5-H triazole), 7.77 (s, 2H, 2-H furan, H-6), 9.89 (brs, 1H, NH). – MS (EI, 70 eV): m/z (%) = 583 (42) [M]+. –
1H, NH), 12.95 (brs, 1H, NH). – 13C NMR ([D6]DMSO): C25H25N7O8S (583.57): calcd. C 51.45, H 4.32, N 16.80;
δ = 47.79, 53.87 (2 NCH2), 57.32 (OCH3), 62.80 (OCH2), found C 51.23, H 4.17, N 16.66.
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