Synthesis of novel 1-hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates and 2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates

Article abstract of DOI:10.1080/10426507.2010.494646

Several new 1-hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates and 2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates as well as the respective phosphonic acids were synthesized from diethyl 1,2-epoxyethylphosphonate and 2,3-epoxypropylphosphonate in the r

Full text of DOI:10.1080/10426507.2010.494646

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Synthesis of Novel 1-Hydroxy-2-
(1,2,3-triazol-1-yl)ethylphosphonates
and 2-Hydroxy-3-(1,2,3-triazol-1-
yl)propylphosphonates
Iwona E. Głowacka a , Marcin Cieślak b & Dorota G. Piotrowska a
a Bioorganic Chemistry Laboratory, Faculty of Pharmacy , Medical
University of Łódź , Poland
b Department of Bioorganic Chemistry , Centre of Molecular and
Macromolecular Studies, Polish Academy of Sciences , Łódź, Poland
Published online: 07 Mar 2011.
To cite this article: Iwona E. Głowacka , Marcin Cieślak & Dorota G. Piotrowska (2011) Synthesis
of Novel 1-Hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates and 2-Hydroxy-3-(1,2,3-triazol-1-
yl)propylphosphonates, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:3, 431-449,
DOI: 10.1080/10426507.2010.494646
To link to this article: http://dx.doi.org/10.1080/10426507.2010.494646
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Phosphorus, Sulfur, and Silicon, 186:431–449, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.494646
SYNTHESIS OF NOVEL 1-HYDROXY-2-(1,2,3-TRIAZOL-1-
YL)ETHYLPHOSPHONATES AND 2-HYDROXY-3-(1,2,3-
TRIAZOL-1-YL)PROPYLPHOSPHONATES
Iwona E. Głowacka,1 Marcin Cies´lak,2
and Dorota G. Piotrowska1
1Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University
of Ło´dz´, Poland
2Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular
Studies, Polish Academy of Sciences, Ło´dz´, Poland
GRAPHICAL ABSTRACT
N
N
OH
N
N
OH
N
N
O
R′
R′
(EtO)2(O)P
(HO)2(O)P
(EtO)2(O)P
n = 0,1
n
n
n
R″
R″
n = 0,1
n = 0,1
Abstract Several new 1-hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates and 2-hydroxy-3-
(1,2,3-triazol-1-yl)propylphosphonates as well as the respective phosphonic acids were synthe-
sized from diethyl 1,2-epoxyethylphosphonate and 2,3-epoxypropylphosphonate in the reaction
sequence including the regioselective ring opening of the epoxide with azides followed by 1,3-
dipolar cycloaddition of ω-azidophosphonates and selected alkynes and finally hydrolyses of
the phosphonate esters.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Azidophosphonates; 1,3-dipolar cycloaddition; 1,4-disubstituted-1,2,3-triazoles;
phosphonic acid
INTRODUCTION
Compoundscontaining 1,2,3-triazole moiety are known to be activate as antibac-
terial,1–4 antifungal,5–7 anticancer,8–10 and antiviral agents.11–13 They were also found
Received 16 April 2010; accepted 15 May 2010.
I.E.G. is grateful to Professor Andrzej E. Wro´blewski for discussions and helpful suggestions during
preparation of this manuscript. Mrs. Małgorzata Pluskota is acknowledged for her excellent technical assistance.
Preliminary experiments in this project were conducted by Elz˙bieta Targowska. This work was supported by
the Medical University of Ło´dz´ internal fund (503-3014-1). The biological part of this work was performed
in the Anticancer Screening Laboratory in the Department of Bioorganic Chemistry, Centre of Molecular and
Macromolecular Studies of the Polish Academy of Sciences and financially supported by the Ministry of Science
and Higher Education through the Centre of Molecular and Macromolecular Studies, Polish Academy of Science,
under Decision PBZ-MNiSW-07/I/2007 for years 2008–2010.
Address correspondence to Iwona E. Głowacka, Bioorganic Chemistry Laboratory, Faculty of Pharmacy,
Medical University of Ło´dz´, Muszyn´skiego 1, 90-151 Ło´dz´, Poland. E-mail: iwona.glowacka@umed.lodz.pl
431

432
I. E. GŁOWACKA ET AL.
to act as β3 adrenegic receptor agonists14 as well as GABA α5 subtype inverse ago-
nists.15 Various molecules having 1,2,3-triazole skeleton with potential biological activity
have been designed so far. The most prominent examples could be found among water-
soluble calixarenes,16 triazole-linked glycoconjugates,17 neoglycopeptides18 and glycopep-
tides,19,20 peptides21 and cyclic peptides,22 enzyme inhibitors,23,24 1,2,3-triazole-modyfied
nucleic acids,25 vitamin D analogues,26,27 1,2,3-triazole dendrimers,28,29 and nucleoside
analogues.30,31
On the other hand, it is known that organophosphorus compounds exhibit interesting
biological properties.32 For example, introduction of a hydrophilic phosphoryl group may
improve solubility and thereby drug delivery to particular targets, as has been found for
steroidal alcohols, which showed better solubility in water after attaching the phosphoryl
residue.33 We reasoned that it is justified to test biological activity of phosphonylated
1,2,3-triazoles.
The conventional method for the synthesis of 1,2,3-triazoles is the Huisgen reaction.
This procedure relies on the 1,3-dipolar cycloaddition of organic azides with alkynes.34,35
While cycloaddition with terminal alkynes under thermal conditions usually gives a mixture
of 1,4- and 1,5-disubstututed regioisomers,36,37 application of copper(I) salts as catalyst
leads to the formation of the 1,4-disubstituted isomers regiospecifically.21,35
This article describes the synthesis of substituted diethyl 2-hydroxy-3-(1,2,3-triazol-
1-yl)propylphosphonates 6, 1-hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates 7, and the
respective acids 8 and 9 as potential cytotoxic and antiviral compounds. They are supposed
to act as acyclic phosphonate analogues of natural nucleotides in which nucleobases are
replaced with substituted 1,2,3-triazole framework. The retrosynthetic analysis for these
compounds is outlined in Scheme 1.
Scheme 1 Retrosynthetic analysis of phosphonylated 1,2,3-triazoles.
RESULTS AND DISCUSSION
To synthesise the 1,2,3-triazoles 6a–6j and 7a–7j, diethyl 2,3-epoxypropylphospho
nate 138,39 and 1,2-epoxyethylphosphonate 240 were first subjected to azidolysis followed
by 1,3-dipolar cycloaddition of the corresponding azidophosphonates with the selected
alkynes.
A
clean transformation of the epoxide
1
to the diethyl 3-azido-2-
hydroxypropylphosphonate 3 has recently been described.41 In a similar way, the
epoxide 2 was transformed into diethyl 2-azido-1-hydroxyethylphosphonate 4 in 85%
yield, and was used in the next step without further purification (Scheme 2).
Phosphonylated 1,2,3-triazoles substituted at C4 with different groups were
obtained employing the 1,3-dipolar cycloaddition (Scheme 3) of azidophosphonates 3
and 4 with terminal alkynes 5a–5h (5a—methyl propiolate, 5b—propargyl benzoate,
5c—phenylacetylene, 5d—1-ethynyl-2-fluorobenzene, 5e—1-ethynyl-3-fluorobenzene,

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
433
Scheme 2 Reagents and conditions: a. NaN3, (NH4)2SO4, MeOH, reflux, 4 h.
5f—1-ethynyl-2,4-difluorobenzene, 5g—1-ethynyl-2-pyridine, 5h—5-ethynyl-1-methyl-
1H-imidazole). The reactions were carried out at room temperature according to a standard
protocol employing Cu(I) as a catalyst, which was generated in situ from CuSO4 and
sodium ascorbate23,28,42 to provide the corresponding 1,2,3-triazoles 6a–6h and 7a–7h in
moderate to excellent yields. The products were finally purified by column chromatography
on silica gel or by crystallization (Scheme 3 and Table 1).
To broaden the structural diversity of phosphonylated 1,2,3-triazole 6i cycloaddition
of diethyl 3-azidophosphonate 3 and 2-cyanoacetamide was performed in the presence
of potassium carbonate and DMSO43 to give 1,2,3-triazole 6i in 75% yield after column
chromatography and crystallization (Scheme 4).
Table 1 Synthesis of substituted 1,2,3-triazoles
Compounds
Rꢁ
Rꢁꢁ Yield (%) Compounds
Rꢁ
Rꢁꢁ
Yield (%)
6a
7a
−COOCH3
H
84
92
6f
7f
H
96
97
6b
7b
−CH2OC(O)Ph
H
H
87
72
6g
7g
H
H
86
94
6c
7c
77
80
6h
7h
67
70
6d
7d
H
H
84
86
6i
7i
C(O)NH2
COOCH3
NH2
84
—
6e
7e
83
94
6j
7j
COOCH3
75
91

434
I. E. GŁOWACKA ET AL.
Scheme 3 Reagents and conditions: a. CuSO4×5H2O (0.05 equiv.), sodium ascorbate (0.1 equiv.), H2O−t-BuOH
(2:1), r.t., 12–24 h.
Scheme 4 Reagents and conditions: a. 2-cyanoacetamide, DMSO, K2CO3, 5 h, 50◦C, 75%.
Futhermore, cycloaddition of azidophosphonates 3 and 4 with dimethyl acetylenedicar-
boxylate was carried out at 110◦C according to the standard procedure44 to give 1,2,3-
triazoles 6j and 7j in 84% and 91% yield, respectively (Scheme 5). Studies on further
functionalization of these diesters are underway in this laboratory.
Scheme 5 Reagents and conditions: a. H3COOCC CCOOCH3, toluene, reflux, 4 h.
Finally, using bromotrimethylsilane diethyl phosphonates 6a–i and 7a–h, j were trans-
formed into the respective phosphonic acids 8a–i and 9a–h, j in good yields43 (Scheme 6
and Table 2).
Scheme 6 Reagents and conditions: a. TMSBr, CH2Cl2, r.t., 72 h.
Compounds 6a–j, 8a and 8f–g were evaluated for their cytotoxicity toward HeLa cells.
After 24 and 48 h incubation with cells, the IC50 values for these compounds were larger

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
435
Table 2 Synthesis of phosphonic acids 8a–i, 9a–h, and 9j
Compounds
Rꢁ
Rꢁꢁ Yield (%) Compounds
Rꢁ
Rꢁꢁ
Yield (%)
8a
9a
−COOCH3
H
95
92
8f
9f
H
95
97
8b
9b
−CH2OC(O)Ph
H
H
93
77
8g
9g
H
H
85
94
8c
9c
90
80
8h
9h
67
70
8d
9d
H
H
85
86
8i
9i
C(O)NH2
COOCH3
NH2
95
—
8e
9e
83
94
8j
9j
COOCH3
—
91
than 1 mM (see the Supplemental Materials, available online). Thus, none of the compounds
displayed noticeable activity toward a selected cell line.
CONCLUSIONS
An efficient method for the synthesis of diethyl 1-hydroxy-2-(1,2,3-triazol-1-
yl)ethylphosphonates and 2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates from
diethyl 1,2-epoxyethylphosphonate and 2,3-epoxypropylphosphonate has been reported.
Clean transformation of the epoxides 1 and 2 to 3-azido-2-hydroxypropylphosphonate 3
and 2-azido-1-hydroxyethylphosphonate 4, respectively, was accomplished using sodium
azide in the presence of ammonium sulfate in refluxing methanol.
The 1,2,3-triazoles 6a–6h and 7a–7h were synthesised from azidophosphonates 3
or 4 by the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition with selected alkynes
5a–h. 1,2,3-Triazoles 6j (7j) and 6i were obtained by reaction azidophosphonates 3 or 4
with dimethyl acetylenedicarboxylate or 2-cyanoacetamide under thermal conditions.
The biological activity of the synthesised phosphonylated 1,2,3-triazoles will be
published in due course.
EXPERIMENTAL
1H NMR spectra were recorded with a Varian Mercury-300 spectrometer; chemical
shifts δ in ppm with respect to TMS; coupling constants J in Hz. 13C and 31P NMR spectra
were recorded on a Varian Mercury-300 machine at 75.5 and 121.5 MHz, respectively.
IR spectral data were measured on an Infinity MI-60 FT-IR spectrometer. Melting points
were determined on a Boetius apparatus and are uncorrected. Elemental analyses were

436
I. E. GŁOWACKA ET AL.
performed by the Microanalytical Laboratory of this faculty on a Perkin Elmer PE 2400
CHNS analyzer.
The following absorbents were used: column chromatography, Merck silica gel 60
(70–230 mesh); analytical TLC, Merck TLC plastic sheets silica gel 60 F254. TLC plates
were developed in chloroform/methanol solvent systems. Visualization of spots was effected
with iodine vapors. All solvents were purified by methods described in the literature.
Diethyl 2,3-epoxypropylphosphonate 138,39 (δ31P 26.71 ppm) and 1,2-
epoxyethylphosphonate 240 (δ31P 19.84 ppm) were prepared according to the literature
procedure in 61% and 60% yields, respectively.
Reaction of Epoxide 1 with Sodium Azide in the Presence of (NH4)2SO4
A mixture of the epoxide 1 (0.826 g, 4.25 mmol), sodium azide (0.664 g, 10.21 mmol),
and ammonium sulfate (1.01 g, 7.65 mmol) in methanol (5 mL) was stirred at 65◦C
for 4 h. After evaporation of solvents, the residue was suspended in ethyl acetate
(5 mL) and filtered through a layer of Celite. The solution was concentrated in vacuo
to give diethyl 3-azido-2-hydroxypropylphosphonate 3 (0.805 g, 80%) as a yellowish oil.
Diethyl 3-Azido-2-hydroxypropylphosphonate 3
1
IR (film) ν [cm−1] 3339, 2985, 2931, 2911, 2105, 1225, 1029; H NMR (C6D6,
300 MHz) δ [ppm]: 0.87 and 0.89 (2t, J = 6.8 Hz, 6H, 2×POCH2CH3), 1.60 (ddd, J =
19.2 Hz, J = 15.0 Hz, J = 3.3 Hz, 1H, H-1b), 1.81 (ddd, J = 16.5 Hz, J = 15.0 Hz, J =
9.6 Hz, 1H, H-1a), 2.02 (brs, 1H, OH), 2.82−2.87 (m, 2H, H-3a, H-3b), 3.72−3.91 (m, 4H,
2×POCH2CH3), 4.03−4.16 (m, 1H, H-2); 13C NMR (CDCl3, 75.5 MHz) δ [ppm]: 16.2 (d,
J = 6.3 Hz, POCC), 30.7 (d, J = 139.4 Hz, C-1), 56.5 (d, J = 14.3 Hz, C-3), 61.7 and 61.9
(2d, J = 6.6 Hz, POC), 65.7 (d, J = 2.9 Hz, C-2); 31P NMR (CDCl3, 121.5 MHz) δ [ppm]
30.18.
Reaction of Epoxide 2 with Sodium Azide in the Presence of (NH4)2SO4
A mixture of the epoxide 2 (2.16 g, 1.20 mmol), sodium azide (1.87 g, 2.88 mmol),
and ammonium sulfate (0.244 g, 1.85 mmol) in methanol (12 mL) was stirred at 65◦C for
4 h. After evaporation of solvents, the residue was suspended in ethyl acetate (5 mL) and
filtered through a layer of Celite. The solution was concentrated in vacuo to give diethyl
2-azido-1-hydroxyethylphosphonate 4 (2.28 g, 85%) as a yellowish oil.
Diethyl 2-Azido-1-hydroxyethylphosphonate 4
IR (film) ν [cm−1] 3310, 2988, 2921, 2135, 1220, 1029; 1H NMR (CDCl3, 300 MHz)
δ [ppm]: 1.35 and 1.36 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 3.40–3.62 (m, 2H, H-2a,
H-2b), 4.05–4.26 (m, 6H, 2×CH3CH2OP, OH, H-1); 31P NMR (CDCl3, 121.5 MHz) δ
[ppm] 22.18.
General Procedure for the Preparation of 1,2,3-Triazoles 6a–h and 7a–h
To a solution of the azidophosphonate (1 mmol) in t-BuOH (0.5 mL) and H2O (1 mL),
CuSO4×5H2O (0.05 mmol), sodium ascorbate (0.1 mmol), and alkynes 5a–h (1 mmol)

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
437
were added. This suspension was stirred vigorously at room temperature for 12–24 h.
After removal of solvents, the residue was suspended in chloroform (15 mL) and filtered
through a layer of Celite. The solution was concentrated in vacuo, and the crude product
was purified by column chromatography on a silica gel column with chloroform/methanol
mixtures or crystallized from ethyl acetate/petroleum ether to give desired 1,2,3-triazoles
6a–h or 7a–h.
Diethyl 2-hydroxy-3-[4-(methoxycarbonyl)-1,2,3-triazol-1-yl]propylphos-
phonate 6a. The target compound was prepared from azidophosphonate 3 (0.248 g,
0.772 mmol) and methyl propiolate (0.069 mL, 0.772 mmol) using the general procedure
described above. The product was purified by crystallization from ethyl acetate/petroleum
ether to give compound 6a (0.282 g, 84%) as a white short needles. Mp: 105–106◦C; IR
1
(KBr) ν [cm−1] 3424, 3287, 2986, 2958, 1725, 1548, 1437, 1237, 1029, 965; H NMR
(CDCl3, 300 MHz) δ [ppm] 1.32 and 1.34 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 1.78
(ddd, J = 16.8 Hz, J = 15.3 Hz, J = 3.0 Hz, 1H, H-1b), 2.00 (ddd, J = 19.2 Hz, J =
15.3 Hz, J = 9.3 Hz, 1H, H-1a), 2.45 (brs, 1H, OH), 3.93 (s, 3H, COOCH3), 4.04–4.19
(m, 4H, 2×POCH2CH3), 4.36–4.51 (m, 2H, H-3b, H-2), 4.59–4.67 (m, 1H, H-3a), 8.31 (s,
1H, HC5 ); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC),
ꢁ
30.8 (d, J = 140.4 Hz, C-1), 52.3 (s, COOCH3), 56.3 (d, J = 17.8 Hz, C-3), 62.2 and 62.4 (2d,
J = 6.6 Hz, 2×POC), 65.3 (d, J = 3.8 Hz, C-2), 129.4 (s, HC C), 139.7 (s, HC C), 161.1
(s, C O); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 29.24; Anal. Calcd. for C11H20N3O6P:
C, 41.12; H, 6.28; N, 13.08. Found: C, 41.18; H, 6.36; N, 12.88.
Diethyl 3-[4-(benzoyloxymethyl)-1,2,3-triazol-1-yl]-2-hydroxypropyl-
phosphonate 6b. The target compound was prepared from azidophosphonate 3 (0.163
g, 0.417 mmol) and propargyl benzoate (0.060 mL, 0.417 mmol) using the general pro-
cedure described above. The product was chromatographed on a silica gel column with
chloroform/methanol (100:1, v/v) to give compound 6b (0.240 g, 87%) as a colorless oil;
IR (film) ν [cm−1] 3338, 2984, 2910, 1720, 1272, 1027, 836, 714; 1H NMR (CDCl3, 300
MHz) δ [ppm] 1.32 and 1.33 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 1.82 (ddd, J = 16.8 Hz,
J = 15.3 Hz, J = 9.0 Hz, 1H, H-1b), 2.01 (ddd, J = 19.5 Hz, J = 15.3 Hz, J = 2.7 Hz, 1H,
H-1a), 2.70 (brs, 1H, OH), 4.05–4.20 (m, 4H, 2×POCH2CH3), 4.36–4.47 (m, 2H, H-3b,
H-2), 4.54–4.61 (m, 1H, H-3a), 5.49 (s, 2H, CH2OC(O)Ph), 7.40–7.45 (m, 2H, Ar H),
13
ꢁ
7.60–7.75 (m, 1H, Ar H), 7.92 (s, 1H, HC5 ), 8.03–8.07 (m, 2H, Ar H); C NMR (CDCl3,
75.5 MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC), 30.8 (d, J = 140.4 Hz, C-1), 56.0
(d, J = 17.4 Hz, C-3), 58.1 (s, CH2OC(O)Ph), 62.3 and 62.4 (2d, J = 7.3 Hz, 2×POC),
65.5 (d, J = 3.8 Hz, C-2), 123.0 (s, HC C) 128.3, 129.6 (Carom.), 133.1 (s, HC C), 142.0
(Cipso), 166.2 (s, C O); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 28.85; Anal. Calcd. for
C17H24N3O6P: C, 51.39; H, 6.09; N, 10.57. Found: C, 51.16; H, 6.18; N, 10.48.
Diethyl 2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propylphosphonate 6c.
The target compound was prepared from azidophosphonate 3 (0.182 g, 0.538 mmol) and
phenylacetylene (0.059 mL, 0.538 mmol) using the general procedure described above.
The product was purified by crystallization from ethyl acetate/petroleum ether to give com-
pound 6c (0.201 g, 77%) as a white amorphous solid. Mp: 86–87◦C; IR (KBr) ν [cm−1
]
1
3327, 2984, 2908, 1227, 1029, 965; H NMR (CDCl3, 300 MHz) δ [ppm] 1.30 and 1.31
(2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 1.85 (ddd, J = 17.1 Hz, J = 15.3 Hz, J = 9.3 Hz,
1H, H-1b), 2.02 (ddd, J = 18.6 Hz, J = 15.3 Hz, J = 3.3 Hz, 1H, H-1a), 4.02–4.17 (m, 5H,
2×POCH2CH3, OH), 4.38–4.50 (m, 2H, H-3b, H-2), 4.56–4.63 (m, 1H, H-3a), 7.29–7.34
ꢁ
(m, 1H, Ar H), 7.37–7.43 (m, 2H, Ar H), 7.79–7.83 (m, 2H, Ar H), 7.99 (s, 1H, HC5 );
13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.4 and 16.5 (2d, J = 6.0 Hz, POCC), 30.8 (d,

438
I. E. GŁOWACKA ET AL.
J = 139.7 Hz, C-1), 56.1 (d, J = 15.9 Hz, C-3), 62.2 and 62.3 (2d, J = 7.3 Hz, 2×POC), 65.5
(d, J = 3.8 Hz, C-2), 121.5 (s, HC C), 125.5, 128.0, 128.6 (Carom.), 130.4 (s, Cipso), 147.3
(HC C); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 28.89; Anal. Calcd. for C15H22N3O4P:
C, 53.09; H, 6.53; N, 12.38. Found: C, 52.96; H, 6.68; N, 12.18.
Diethyl 3-[4-(2-fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphos-
phonate 6d. The target compound was prepared from azidophosphonate 3 (0.183 g, 0.513
mmol) and 1-ethynyl-2-fluorobenzene (0.058 mL, 0.513 mmol) using the general procedure
described above. The product was purified by crystallization from ethyl acetate/petroleum
ether to give compound 6d (0.232 g, 84%) as a white solid. Mp: 79–80◦C; IR (KBr) ν
[cm−1] 3339, 2984, 2911, 1478, 1221, 1028, 967, 818, 762; 1H NMR (CDCl3, 300 MHz)
δ [ppm] 1.33 and 1.34 (2t, J = 6.9 Hz, 6H, 2×POCH2CH3), 1.83 (ddd, J = 16.5 Hz, J =
15.3 Hz, J = 9.3 Hz, 1H, H-1b), 1.80 (brs, 1H, OH), 2.03 (ddd, J = 18.6 Hz, J = 15.3 Hz,
J = 3.3 Hz, 1H, H-1a), 4.06–4.21 (m, 4H, 2×CH3CH2OP), 4.41–4.66 (m, 3H, H-2, H-3a,
H-3b), 7.14 (ddd, J = 10.8 Hz, J = 7.8 Hz, J = 1.2 Hz, 1H, Ar H), 7.22–7.35 (m, 2H,
Ar H), 8.14 (d, J = 3.6 Hz, HC5 ), 8.28 (dt, J = 7.8 Hz, J = 1.8 Hz, 1H, Ar H); 13C NMR
ꢁ
(CDCl3, 75.5 MHz) δ [ppm] 16.4 and 16.5 (2d, J = 6.8 Hz, POCC), 31.0 (d, J = 140.3 Hz,
C-1), 56.2 (d, J = 16.9 Hz, C-3), 62.3 and 62.4 (2d, J = 6.6 Hz, POC), 65.6 (d, J = 3.1 Hz
C-2), 115.7 (d, J = 21.8 Hz, C-3arom.), 118.5 (d, J = 12.9 Hz, C-1arom.), 124.6 (d, J = 12.6
Hz, Carom.), 124.6 (d, J = 3.4 Hz, Carom.), 127.6 (d, J = 3.4 Hz, HC = C), 129.2 (d, J =
8.6 Hz, C-4arom.), 141.0 (s, C CH), 159.1 (d, J = 247.6 Hz, C F); 31P NMR (CDCl3,
121.5 MHz) δ [ppm] 28.91. Anal. Calcd. for C15H21FN3O4P: C, 50.42; H, 5.92; N, 11.76.
Found: C, 50.44; H, 5.96; N, 11.62.
Diethyl 3-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphos-
phonate 6e. The target compound was prepared from azidophosphonate 3 (0.175 g, 0.489
mmol) and 1-ethynyl-3-fluorobenzene (0.056 mL, 0.489 mmol) using the general procedure
described above. The product was chromatographed on a silica gel column with chloro-
form/methanol (100:1, v/v) to give compound 6e (0.218 g, 83%) as a colorless oil; IR (film)
1
ν [cm−1] 3326, 3141, 2985, 2911, 1466, 1229, 1030, 967, 866, 787; H NMR (CDCl3,
300 MHz) δ [ppm] 1.33 and 1.35 (2t, J = 6.9 Hz, 6H, 2×POCH2CH3), 1.80
(ddd, J = 16.8 Hz, J = 15.3 Hz, J = 9.6 Hz, 1H, H-1b), 1.85 (brs, 1H, OH),
1.97–2.09 (m, 1H, H-1a), 4.05–4.21 (m, 4H, 2×POCH2CH3), 4.39–4.51 (m, 2H,
H-2, H-3b), 4.56–4.66 (m, 1H, H-3a), 6.99–7.06 (m, 1H, Ar H), 7.35–7.42 (m,
1H, Ar H), 7.55–7.62 (m, 2H, Ar H), 8.01 (s, 1H, HC5 ); 13C NMR (CDCl3,
ꢁ
75.5 MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC), 30.9 (d, J =
140.0 Hz, C-1), 56.2 (d, J = 17.2 Hz, C-3), 62.4 and 62.5 (2d, J = 6.9 Hz, POC),
65.6 (d, J = 3.7 Hz C-2), 112.7 (d, J = 22.9 Hz, C-2arom.), 114.9 (d, J = 21.2 Hz, Carom.),
121.3 (d, J = 2.9 Hz, Carom.), 122.1 (s, HC C) 130.5 (d, J = 8.3 Hz, Carom.), 146.4 (s,
C CH), 163.1 (d, J = 245.1 Hz, C F); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 28.93.
Anal. Calcd. for C15H21FN3O4P×0.25 H2O: C, 49.79; H, 5.99; N, 11.61. Found: C, 49.62;
H, 5.79; N, 11.64.
Diethyl 3-[4-(2,4-difluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropyl-
phosphonate 6f. The target compound was prepared from azidophosphonate 3 (0.118
g, 0.314 mmol) and 1-ethynyl-2,4-difluorobenzene (0.043 g, 0.314 mmol) using the gen-
eral procedure described above. The product was purified by crystallization from ethyl ac-
etate/petroleum ether to give compound 6f (0.179 g, 96%) as a white solid. Mp: 129–130◦C;
IR (KBr) ν [cm−1] 3286, 3136, 2988, 2907, 1628, 1600, 1561, 1493, 1196, 1072, 1036,
1
979, 826; H NMR (CDCl3, 300 MHz) δ [ppm] 1.33 and 1.34 (2t, J = 6.9 Hz, 6H,
2×POCH2CH3), 1.80 (brs, 1H, OH), 1.83 (ddd, J = 16.8 Hz, J = 15.3 Hz, J = 9.3 Hz,

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
439
1H, H-1b), 2.03 (ddd, J = 19.2 Hz, J = 15.3 Hz, J = 3.0 Hz, 1H, H-1a), 4.06–4.21 (m,
4H, 2×POCH2CH3), 4.40–4.66 (m, 3H, H-2, H-3a, H-3b), 6.87–7.03 (m, 2H, Ar H),
ꢁ
7.35–7.42 (m, 1H, Ar H), 8.09 (d, J = 3.9 Hz, HC5 ), 8.26 (dt, J = 8.4 Hz, J = 6.3 Hz,
1H, Ar H); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC),
30.9 (d, J = 140.4 Hz, C-1), 56.2 (d, J = 17.4 Hz, C-3), 62.3 and 62.5 (2d, J = 6.8 Hz,
POC), 65.6 (d, J = 3.8 Hz, C-2), 104.1 (t, J = 30.2 Hz, C-3arom.), 112.0 (dd, J = 21.2 Hz,
J = 3.4 Hz, C-1arom.), 115.0 (dd, J = 13.2 Hz, J = 3.7 Hz, C-5arom.), 124.1 (d, J = 12.0
Hz, C-6arom.), 128.6 (dd, J = 9.7 Hz, J = 5.2 Hz, HC C), 140.4 (s, C C Ph), 159.2 (dd,
J = 249.2 Hz, J = 12.3 Hz, C-2arom.), 162.4 (dd, J = 249.2 Hz, J = 12.6 Hz, C-4arom.); 31
P
NMR (CDCl3, 121.5 MHz) δ [ppm] 29.65. Anal. Calcd. for C15H20F2N3O4P: C, 48.00; H,
5.37; N, 11.20. Found: C, 48.01; H, 5.29; N, 11.09.
Diethyl 2-hydroxy-3-[4-(pyridin-2-yl)-1,2,3-triazol-1-yl]propylphos-
phonate 6g. The target compound was prepared from azidophosphonate 3 (0.224 g,
0.660 mmol) and 1-ethynyl-2-pyridine (0.067 mL, 0.660 mmol) using the general pro-
cedure described above. The product was chromatographed on a silica gel column with
chloroform/methanol (50:1, v/v) to give compound 6g (0.277 g, 86%) as a colorless oil;
IR (film) ν [cm−1] 3339, 3104, 2925, 2851, 1636, 1612, 1226, 1163, 1080, 786; 1H NMR
(CDCl3, 300 MHz) δ [ppm] 1.34 and 1.37 (2t, J = 7.0 Hz, 6H, 2×POCH2CH3), 1.91–2.22
(m, 2H, H-1b, H-1a), 4.05–4.21 (m, 4H, 2× POCH2CH3), 4.21–4.59 (m, 3H, H-2, H-3b,
OH), 4.61 (dd, J = 14.2 Hz, J = 4.0 Hz, 1H, H-3a), 7.22–7.26 (m, 1H, Ar H), 7.80 (dt,
ꢁ
J = 7.8 Hz, J = 1.8 Hz, 1H, Ar H), 8.16 (d, J = 7.8 Hz, 1H, Ar H), 8.38 (s, 1H, HC5 ),
8.37–8.60 (m 1H, Ar H); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.6 and 16.7 (2d, J =
6.0 Hz, POCC), 31.0 (d, J = 140.4 Hz, C-1), 56.3 (d, J = 17.4 Hz, C-3), 62.3 and 62.5 (2d,
J = 6.0 Hz, POC), 65.7 (d, J = 3.7 Hz, C-2), 120.4 (s, Carom.), 123.0 (s, HC C), 124.0,
137.2 (s, Carom.), 147.9 (s, C CH), 149.2, 150.1 (s, Carom.); 31P NMR (CDCl3, 121.5 MHz)
δ [ppm] 28.85. Anal. Calcd. for C14H21N4O4P×H2O: C, 46.92; H, 6.47; N, 15.64. Found:
C, 47.06; H, 6.34; N, 15.41.
Diethyl 2-hydroxy-3-[4-(1-methyl-1H-imidazol-5-yl)-1,2,3-triazol-1-yl]
propylphosphonate 6h. The target compound was prepared from azidophosphonate
3 (0.186 g, 0.541 mmol) and 5-ethynyl-1-methyl-1H-imidazole (0.055 mL, 0.541 mmol)
using the general procedure described above. The product was chromatographed on a silica
gel column with chloroform/methanol (50:1 to 20:1 v/v) to give compound 6h (0.180 g,
67%) as a colorless oil; IR (film) ν [cm−1] 3392, 2985, 2911, 1656, 1629, 1510, 1230,
1029, 966, 833; 1H NMR (CDCl3, 300 MHz) δ [ppm] 1.34 and 1.35 (2t, J = 6.9 Hz, 6H,
2×POCH2CH3), 1.84–2.12 (m, 2H, H-1a, H-1b), 3.05 (brs, 1H, OH), 3.91 (s, 3H, CH3 N),
4.07–4.21 (m, 4H, 2×POCH2CH3), 4.39–4.51 (m, 2H, H-2, H-3b), 4.60–4.68 (m, 1H, H-
3a), 7.20 (brs, 1H, Himid), 7.56 (brs, 1H, Himid), 7.94 (s, 1H, HC5 ); 13C NMR (CDCl3,
ꢁ
75.5 MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC), 31.3 (d, J = 140.0 Hz, C-1),
33.8 (s, CH3 N), 56.4 (d, J = 16.0 Hz, C-3), 62.2 and 62.4 (2d, J = 6.6 Hz, POC), 65.4 (d,
J = 3.1 Hz, C-2), 122.7, 123.6, 127.8 (s, HC C), 137.9 (s, HC C), 139.1 (s, N CH N);
31P NMR (CDCl3, 121.5 MHz) δ [ppm] 28.70. Anal. Calcd. for C13H22N5O4P: C, 45.48;
H, 6.46; N, 20.40. Found: C, 45.44; H, 6.21; N, 20.61.
Diethyl 1-hydroxy-2-[4-(methoxycarbonyl)-1,2,3-triazol-1-yl]ethylphos-
phonate 7a. The target compound was prepared from azidophosphonate 4 (0.118 g,
0.383 mmol) and methyl propiolate (0.034 mL, 0.383 mmol) using the general procedure
described above. The product was purified by crystallization from ethyl acetate/petroleum
ether to give compound 7a (0.149 g, 92%) as white needles. Mp: 117–119◦C; IR (KBr)
1
ν [cm−1] 3262, 3106, 2986, 2987, 1723, 1549, 1245, 1224, 1024; H NMR (CDCl3,

440
I. E. GŁOWACKA ET AL.
300 MHz) δ [ppm] 1.33 and 1.34 (2t, J = 6.9 Hz, 6H, 2×POCH2CH3), 3.93 (s, 3H,
COOCH3), 4.17–4.22 (m, 5H, 2×POCH2CH3, OH), 4.29 (ddd, J = 9.9 Hz, J = 7.8 Hz, J
= 2.7 Hz, 1H, H-1), 4.50 (ddd, J = 14.1 Hz, J = 9.9 Hz, J = 5.4 Hz, 1H, H-2a), 4.87 (ddd,
J = 14.1 Hz, J = 5.4 Hz, J = 2.7 Hz, 1H, H-2b), 8.32 (s, 1H, HC5 ); 13C NMR (CDCl3,
ꢁ
75.5 MHz) δ [ppm] 16.6 and 16.7 (2d, J = 6.0 Hz, POCC), 52.3 (s, COOCH3), 63.7 and
63.8 (2d, J = 6.8 Hz, 2×POC), 66.7 (d, J = 165.3 Hz, C-1), 129.5 (s, HC C), 139.4 (s,
HC C), 161.0 (s, C O); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 20.85; Anal. Calcd. for
C10H18N3O6P: C, 39.09; H, 5.90; N, 13.68. Found: C, 39.07; H, 5.79; N, 13.78.
Diethyl 2-[4-(benzoyloxymethyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphos-
phonate 7b. The target compound was prepared from azidophosphonate 4 (0.234 g,
0.634 mmol) and propargyl benzoate (0.092 mL, 0.634 mmol) using the general procedure
described above. The crude product was chromatographed on a silica gel column with chlo-
roform/methanol (100:1, v/v), and the appropriate fractions were crystallized from ethyl
acetate/hexane to give compound 7b (0.300 g, 72%) as a white powder. Mp: 104–105◦C;
1
IR (KBr) ν [cm−1] 3328, 2982, 2890, 1722, 1268, 1025, 843, 720; H NMR (CDCl3,
300 MHz) δ [ppm] 1.32 and 1.33 (2t, J = 6.9 Hz, 6H, 2×POCH2CH3), 4.09–4.22 (m, 5H,
2×POCH2CH3, OH), 4.24–4.36 (m, 1H, H-1), 4.42–4.61 (m, 1H, H-2b), 4.78–4.84 (m, 1H,
H-2a), 5.49 (s, 2H, CH2OC(O)Ph), 7.40–7.45 (m, 2H, Ar H), 7.48–7.60 (m, 1H, Ar H),
7.92 (s, 1H, HC5 ), 8.03–8.10 (m, 2H, Ar H); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.6
ꢁ
and 16.7 (2d, J = 5.7 Hz, POCC), 51.8 (s, C-2), 58.2 (s, CH2OC(O)Ph), 63.6 and 63.8 (2d,
J = 7.2 Hz, 2×POC), 67.1 (d, J = 163.5 Hz, C-1), 123.0 (s, HC C) 128.4, 129.8 (Carom.),
133.3 (s, HC C), 140.2 (Cipso), 166.4 (s, C O); 31P NMR (CDCl3, 121.5 MHz) δ [ppm]
20.97; Anal. Calcd. for C16H22N3O6P: C, 50.13; H, 5.78; N, 10.96. Found: C, 49.98; H,
5.75; N, 11.04.
Diethyl 1-hydroxy-2-(4-phenyl-1,2,3-triazol-1-yl)ethylphosphonate 7c.
The target compound was prepared from azidophosphonate 4 (0.123 g, 0.379 mmol) and
phenylacetylene (0.042 mL, 0.379 mmol) using the general procedure described above.
The product was purified by crystallization from ethyl acetate/petroleum ether to give
compound 7c (0.144 g, 80%) as a white amorphous solid. Mp: 92–94◦C IR (KBr) ν [cm−1
]
1
3252, 3084, 2986, 1223, 1015, 976, 765, 692; H NMR (CDCl3, 300 MHz) δ [ppm]
1.35 and 1.36 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 4.15–4.27 (m, 4H, 2×POCH2CH3),
4.46–4.57 (m, 3H, H-2a, H-2b, OH), 4.85 (ddd, J = 13.8 Hz, J = 7.8 Hz, J = 2.1 Hz,
1H, H-1), 7.27–7.39 (m, 3H, Ar H), 7.69–7.72 (m, 2H, Ar H), 7.92 (s, 1H, HC5 ); 13C
ꢁ
NMR (CDCl3, 75.5 MHz) δ [ppm] 16.6 and 16.7 (2d, J = 5.3 Hz, POCC), 52.1 (d, J =
10.6 Hz, C-2), 63.4 and 63.5 (2d, J = 6.8 Hz, 2×POC), 67.0 (d, J = 165.3 Hz, C-1),
121.8, 125.5, 128.1, 128.8 (Carom.), 130.4 (HC C), 147.0 (HC C); 31P NMR (CDCl3,
121.5 MHz) δ [ppm] 21.25; Anal. Calcd. for C14H20N3O4P: C, 51.69; H, 6.20; N, 12.92.
Found: C, 51.45; H, 6.22; N, 13.00.
Diethyl 2-[4-(2-fluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphospho-
nate 7d. The target compound was prepared from azidophosphonate 4 (0.308 g, 0.898
mmol) and 1-ethynyl-2-fluorobenzene (0.102 mL, 0.898 mmol) using the general procedure
described above. The product was purified by crystallization from ethyl acetate/petroleum
ether to give compound 7d (0.408 g, 86%) as a white solid. Mp: 100–101◦C; IR (KBr) ν
1
[cm−1] 3236, 2991, 2909, 1487, 1210, 1048, 760; H NMR (CDCl3, 300 MHz) δ [ppm]
1.35 and 1.37 (2t, J = 6.9 Hz, 6H, 2×POCH2CH3), 4.16–4.28 (m, 5H, 2×CH3CH2OP,
OH), 4.43–4.60 (m, 2H, H-2a, H-1), 4.87 (ddd, J = 13.9 Hz, J = 5.6 Hz, J = 2.4 Hz,
1H, H-2b), 7.02–7.08 (m, 1H, Ar H), 7.19–7.31 (m, 2H, Ar H), 8.12 (d, J = 3.8 Hz,
1H, HC5 ), 8.15–8.21 (m, 1H, Ar H); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.6 and
ꢁ

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
441
16.7 (2d, J = 5.4 Hz, POCC), 52.0 (d, J = 10.3 Hz, C-2), 63.5 and 63.6 (2d, J = 7.2
Hz, 2×POC), 67.2 (d, J = 164.9 Hz, C-1), 115.6 (d, J = 21.8 Hz, C-3arom.), 118.2 (d,
J = 12.6 Hz, C-1arom.), 124.6 (d, J = 3.4 Hz, C-5arom.), 124.8 (d, J = 12.6 Hz, Carom.),
127.4 (d, J = 3.4 Hz, HC C), 129.4 (d, J = 8.6 Hz, Carom.), 140.6 (s, HC C), 158.8 (d,
J = 247.6 Hz, F−Carom.); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 21.45. Anal. Calcd. for
C14H19FN3O4P: C, 48.98; H, 5.58; N, 12.24. Found: C, 48.99; H, 5.38; N, 12.29.
Diethyl 2-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphospho-
nate 7e. The target compound was prepared from azidophosphonate 4 (0.333 g, 0.971
mmol) and 1-ethynyl-3-fluorobenzene (0.112 mL, 0.971 mmol) using the general procedure
described above. The product was chromatographed on a silica gel column with chloro-
form/methanol (100:1, v/v) to give compound 7e (0.482 g, 94%) as a white amorphous
solid. Mp: 82–83◦C; IR (KBr) ν [cm−1] 3316, 3101, 2991, 1476, 1225, 1022, 777; 1H
NMR (CDCl3, 300 MHz) δ [ppm] 1.36 and 1.37 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3),
4.16–4.28 (m, 4H, 2×POCH2CH3), 4.40–4.57 (m, 3H, H-2, H-1b, OH), 4.83–4.90 (m, 1H,
H-1a), 6.99–7.04 (m, 1H, Ar H), 7.31–7.52 (m, 3H, Ar H), 7.98 (s, 1H, HC5 ); 13C NMR
ꢁ
(CDCl3, 75.5 MHz) δ [ppm] 16.4 and 16.5 (2d, J = 5.3 Hz, POCC), 52.1 (d, J = 9.3 Hz,
C-2), 63.5 and 63.6 (2d, J = 7.2 Hz, POC), 67.0 (d, J = 165.2 Hz, C-1), 112.3 (d, J = 22.6
Hz, Carom.), 114.9 (d, J = 19.6 Hz, Carom..), 121.1 (d, J = 2.9 Hz, Carom.), 122.2 (s, HC C)
130.4 (d, J = 8.6 Hz, Carom.), 132.3 (d, J = 8.3 Hz, C-1arom.), 146.4 (s, C CH), 163.1 (d,
J = 245.2 Hz, F Carom.); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 21.19. Anal. Calcd. for
C14H19FN3O4P: C, 48.98; H, 5.58; N, 12.24. Found: C, 49.15; H, 5.51; N, 12.18.
Diethyl 2-[4-(2,4-difluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphos-
phonate 7f. The target compound was prepared from azidophosphonate 4 (0.239 g,
0.661 mmol) and 1-ethynyl-2,4-difluorobenzene (0.091 g, 0.661 mmol) using the general
procedure described above. The product was purified by crystallization from ethyl
acetate/petroleum ether to give compound 7f (0.375 g, 97%) as a white solid; m.p.:
136–137◦C; IR (KBr) ν [cm−1] 3243, 2986, 2911, 1493, 1226, 1046, 979, 816; 1H NMR
(CDCl3, 300 MHz) δ [ppm] 1.36 and 1.39 (2t, J = 7.2 Hz, 6H, 2×POCH2CH3), 4.16–4.31
(m, 5H, 2×POCH2CH3, OH), 4.43 (ddd, J = 9.6 Hz, J = 8.4 Hz, J = 2.4 Hz, 1H, H-1),
4.58 (ddd, J = 14.1 Hz, J = 9.6 Hz, J = 5.4 Hz, 1H, H-2b), 4.89 (ddd, J = 14.1 Hz,
J = 6.3 Hz, J = 2.4 Hz, 1H, H-2a), 6.84–6.92 (m, 1H, Ar H), 6.95–7.02 (m, 1H, Ar H),
8.07 (d, J = 3.6 Hz, HC5 ), 8.19–8.26 (m, 1H, Ar H); 13C NMR (CDCl3, 75.5 MHz) δ
ꢁ
[ppm] 16.6 and 16.7 (2d, J = 5.3 Hz, POCC), 52.0 (d, J = 10.0 Hz, C-2), 63.5 and 63.6
(2d, J = 7.2 Hz, POC), 67.2 (d, J = 164.6 Hz, C-1), 104.0 (t, J = 25.8 Hz, C-3arom.), 112.0
(dd, J = 21.2 Hz, J = 3.2 Hz, C-1arom.), 114.8 (dd, J = 13.2 Hz, J = 3.7 Hz, C-5arom.),
124.4 (d, J = 12.6 Hz, HC C), 128.4 (dd, J = 9.4 Hz, J = 5.2 Hz, C-6arom.), 140.0 (s,
HC C), 159.1 (dd, J = 254.2 Hz, J = 12.9 Hz, C-2arom.), 162.5 (dd, J = 252.5 Hz,
J = 12.6 Hz, C-4arom.); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 21.02. Anal. Calcd. for
C14H18F2N3O4P: C, 46.54; H, 5.02; N, 11.63. Found: C, 46.33; H, 4.83; N, 11.62.
Diethyl
1-hydroxy-2-[4-(pyridin-2-yl)-1,2,3-triazol-1-yl]ethylphospho-
nate 7g. The target compound was prepared from azidophosphonate 4 (0.307 g, 0.941
mmol) and 1-ethynyl-2-pyridine (0.095 mL, 0.941 mmol) using the general procedure
described above. The product was purified by crystallization from ethyl acetate/petroleum
ether to give compound 7g (0.422 g, 94%) as a white powder. Mp: 105–106◦C; IR (KBr) ν
[cm−1] 3254, 2985, 2931, 1606, 1222, 1023, 975, 786; 1H NMR (CDCl3, 300 MHz) δ [ppm]
1.36 and 1.40 (2t, J = 7.1 Hz, 6H, 2×POCH2CH3), 2.80 (brs, 1H, OH), 4.19–4.33 (m, 4H,
2× POCH2CH3), 4.44 (ddd, J = 10.4 Hz, J = 8.3 Hz, J = 2.4 Hz, 1H, H-1), 4.58 (ddd,
J = 14.1 Hz, J = 10.4 Hz, J = 5.2 Hz, 1H, H-2b), 4.92 (ddd, J = 14.1 Hz, J = 4.7 Hz,

442
I. E. GŁOWACKA ET AL.
J = 2.4 Hz, 1H, H-2a), 7.10–7.18 (m, 1H, Ar H), 7.80 (dt, J = 8.1 Hz, J = 1.5 Hz, 1H,
ꢁ
Ar H), 8.12 (d, J = 8.1 Hz, 1H, Ar H), 8.45 (s, 1H, HC5 ), 8.50 (d, J = 4.5 Hz, 1H,
Ar H); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.6 and 16.7 (2d, J = 5.7 Hz, POCC),
52.3 (d, J = 10.9 Hz, C-2), 63.3 and 63.4 (2d, J = 8.6 Hz, POC), 67.4 (d, J = 166.1
Hz, C-1), 120.5 (s, Carom.), 122.9 (s, Carom.), 124.2 (HC C), 137.2 (s, Carom.), 147.0 (s,
C CH), 148.8 (s, Carom.), 149.6 (s, Cipso); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 21.29.
Anal. Calcd. for C13H19N4O4P×1/2H2O: C, 46.57; H, 6.01; N, 16.71. Found: C, 46.33; H,
5.98; N, 16.62.
Diethyl1-hydroxy-2-[4-(1-methyl-1H-imidazol-5-yl)-1,2,3-triazol-1-yl]ethyl
phosphonate 7h. The target compound was prepared from azidophosphonate 4 (0.292
g, 0.888 mmol) and 5-ethynyl-1-methyl-1H-imidazole (0.090 mL, 0.888 mmol) using the
general procedure described above. The product was chromatographed on a silica gel
column with chloroform/methanol (50:1 to 20:1 v/v), and the appropriate fractions were
crystallized from methanol/diethyl ether to give compound 7h (0.302 g, 70%) as white
short needles. Mp: 162–163◦C; IR (KBr) ν [cm−1] 3441, 3092, 2985, 2921, 2852, 1252,
1090, 1030, 976; 1H NMR (CDCl3, 300 MHz) δ [ppm] 1.36 and 1.37 (2t, J = 7.2 Hz, 6H,
2×POCH2CH3), 3.84 (s, 3H, CH3 N), 4.19–4.29 (m, 5H, 2×POCH2CH3, OH), 4.35 (dt,
J = 10.3 Hz, J = 2.4 Hz, 1H, H-1), 4.51 (ddd, J = 13.8 Hz, J = 10.3 Hz, J = 5.1 Hz, 1H,
H-2b), 4.89 (ddd, J = 13.8 Hz, J = 3.9 Hz, J = 2.4 Hz, 1H, H-2a), 6.98 (brs, 1H, Himid),
7.38 (brs, 1H, Himid), 7.87 (s, 1H, HC5 ); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.7 and
ꢁ
16.8 (2d, J = 5.4 Hz, POCC), 33.9 (s, CH3 N), 52.4 (d, J = 10.9 Hz, C-2), 63.2 and 63.4
(2d, J = 7.5 Hz, POC), 66.9 (d, J = 166.8 Hz C-1), 122.8, 123.6, 127.3 (s, HC C), 137.4
(s, HC C), 138.9 (s, N CH N); 31P NMR (CDCl3, 121.5 MHz) δ [ppm] 21.45. Anal.
Calcd. for C12H20N5O4P: C, 43.77; H, 6.12; N, 21.27. Found: C, 43.73; H, 6.13; N, 21.37.
Preparation of Diethyl 2-Hydroxy-3-(4,5-dimethoxycarbonyl-1,2,3-
triazol-1-yl)propylphosphonate 6i
A solution of the azide 3 (0.207g, 0.873 mmol) and dimethyl acetylenedicarboxy-
late (0.107 mL, 0.873 mmol) in toluene (2 mL) was refluxed for 4 h. The mixture was
concentrated to dryness to leave a yellow solid (0.345 g), which was chromatographed
on a silica gel column with chloroform/methanol (100:1, v/v) and later crystallized from
ethyl acetate/petroleum ether to give phosphonate 6i (0.277 g, 84%) as a white solid. Mp:
85–86◦C; IR (KBr): ν [cm−1] 3302, 2986, 2957, 2911, 1737, 1468, 1440, 1224, 1025,
1
963, 826, 754; H NMR (CDCl3, 300 MHz) δ [ppm] 1.33 and 1.34 (2t, J = 6.9 Hz, 6H,
2×POCH2CH3), 1.80 (ddd, J = 16.5 Hz, J = 15.3 Hz, J = 9.9 Hz, 1H, H-1a), 2.04 (ddd,
J = 18.3 Hz, J = 15.3 Hz, J = 3.0 Hz, 1H, H-1b), 3.98 (s, 3H, COOCH3), 3.99 (s, 3H,
COOCH3), 4.01 (d, J = 3.0 Hz, 1H, OH), 4.05–4.24 (m, 4H, 2×POCH2CH3), 4.31–4.50
(m, 1H, H-2), 4.70 (dd, J = 13.8 Hz, J = 6.6 Hz, 1H, H-3a), 4.82 (ddd, J = 13.8 Hz, J =
3.9 Hz, J = 1.5 Hz, 1H, H-3b); 13C NMR (CDCl3, 75.5 MHz) δ [ppm] 16.5 and 16.6 (2d,
J = 6.0 Hz, POCC), 30.9 (d, J = 140.4 Hz, C-1), 52.8 (s, COOCH3), 56.3 (s, COOCH3),
55.3 (d, J = 18.9 Hz, C-3), 62.4 and 62.6 (2d, J = 6.8 Hz, 2×POC), 65.6 (d, J = 3.8
Hz, C-2), 132.1 (s, HC C), 139.2 (s, HC C), 159.3 (s, C O), 160.3 (s, C O); 31P NMR
(CDCl3, 121.5 MHz) δ [ppm] 29.21; Anal. Calcd. for C13H22N3O8P: C, 41.16; H, 5.84; N,
11.08. Found: C, 41.25; H, 5.66; N, 11.08.

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
443
Preparation of Diethyl 3-(5-Amino-4-carbamoyl-1,2,3-
triazol-1-yl)-2-hydroxypropylphosphonate 6j
To a solution of 2-cyanoacetamide (0.203 g, 2.42 mmol) in DMSO (1.0 mL), K2CO3
(0.334 g, 2.42 mmol) was added at room temperature under an argon atmosphere. The
mixture was stirred at the same temperature for 30 min. After addition of diethyl 3-azido-
2-hydroxypropylphosphonate 3 (0.286 g, 1.20 mmol) in DMSO (0.7 mL), the stirring was
continued for 5 h at 50 ◦C. After evaporation of the solvent, the residue was purified by silica
gel column chromatography with chloroform/methanol (20:1, 10:1 v/v), and the appropriate
fractions were crystallized from ethyl acetate/petroleum ether to afford 6j (0.341 g, 75%)
as a white amorphous solid. Mp: 155–157◦C; IR (KBr) ν [cm−1] 3486, 3366, 3193, 2956,
2911, 1665, 1638, 1239, 1030, 949; 1H NMR (CDCl3, 300 MHz) δ [ppm] 1.33 and 1.35 (2t,
J = 6.9 Hz, 6H, 2×POCH2CH3), 1.81 (ddd, J = 16.2 Hz, J = 15.3 Hz, J = 10.5 Hz, 1H,
H-1b), 2.02 (ddd, J = 19.2 Hz, J = 15.3 Hz, J = 3.0 Hz, 1H, H-1a), 2.70 (brs, 1H, OH),
4.05–4.42 (m, 4H, 2×POCH2CH3), 4.26 (dd, J = 14.4 Hz, J = 5.1 Hz, H-3b), 4.35–4.50
(m, 2H, H-2, H-3a), 5.79 (brs, 2H, C(O)NH2), 5.48 and 6.74 (2 × brs, 2H, NH2); 13C NMR
(CDCl3, 75.5 MHz) δ [ppm] 16.6 and 16.7 (2d, J = 5.3 Hz, POCC), 30.3 (d, J = 139.7
Hz, C-1), 52.6 (d, J = 18.9 Hz, C-3), 62.7 and 62.8 (2d, J = 6.8 Hz, 2×POC), 67.0 (d, J =
3.0 Hz, C-2), 123.0 (s, HC C), 146.5 (s, HC C), 164.6 (s, C O); 31P NMR (CDCl3,
121.5 MHz) δ [ppm] 29.87; Anal. Calcd. for C10H20N5O5P: C, 37.39; H, 6.28; N, 21.80.
Found: C, 37.54; H, 6.29; N, 21.68.
Preparation of Diethyl 1-Hydroxy-2-(4,5-dimethoxycarbonyl-1,2,3-
triazol-1-yl)ethylphosphonate 7j
A solution of the azide 4 (0.171g, 0.766 mmol) and dimethyl acetylenedicarboxylate
(0.094 mL, 0.766 mmol) in toluene (2 mL) was refluxed for 4 h. The mixture was con-
centrated to dryness to leave a yellow solid (0.311 g), which was chromatographed on a
silica gel column with chloroform/methanol (100:1, v/v) and later crystallized from ethyl
acetate/diethyl ether to give phosphonate 7j (0.256 g, 91%) as a white solid. Mp: 97–98◦C;
IR (KBr): ν [cm−1] 3233, 2963, 2914, 1732, 1230, 1052, 963; 1H NMR (CDCl3, 300 MHz)
δ [ppm] 1.33 and 1.34 (2t, J = 7.1 Hz, 6H, 2×POCH2CH3), 3.95 (s, 3H, COOCH3), 3.97
(s, 3H, COOCH3), 4.10–4.21 (m, 5H, 2×POCH2CH3, OH), 4.32 (ddd, J = 7.8 Hz, J =
7.0 Hz, J = 5.7 Hz, 1H, H-1), 4.83–4.94 (m, 2H, H-2a, H-2b); 13C NMR (CDCl3, 75.5
MHz) δ [ppm] 16.5 and 16.6 (2d, J = 6.0 Hz, POCC), 51.1 (d, J = 10.2 Hz, C-2), 52.8 (s,
COOCH3), 53.4 (s, COOCH3), 63.2 and 63.6 (2d, J = 7.2 Hz, 2×POC), 66.8 (d, J = 164.4
Hz, C-1), 131.8 (s, HC C), 139.1 (s, HC C), 158.9 (s, C O), 160.2 (s, C O); 31P NMR
(CDCl3, 121.5 MHz) δ [ppm] 20.65; Anal. Calcd. for C12H20N3O8P: C, 39.46; H, 5.52; N,
11.50. Found: C, 39.37; H, 5.37; N, 11.61.
Deprotection of the Diethyl Phosphonate into 6a–i and 7a–h, j,
General Procedure
Solutions of diethyl phosphonates 6a–i (1 mmol) in CH2Cl2 (0.5 mL) were treated
with bromotrimethylsilane (10 mmol) at room temperature under argon atmosphere. The
reaction mixture was protected from light and stirred at room temperature for 24 h. After

444
I. E. GŁOWACKA ET AL.
concentration to dryness, the residue was co-evaporated with dichloromethane (5 mL) and
ethanol (3 × 3 mL) to afford crude phosphonic acids 8a–i.
2-Hydroxy-3-[4-(methoxycarbonyl)-1,2,3-triazol-1-yl]propylphosphonic
acid 8a. Compound 8a was obtained as a white powder (0.056 g, 95%), which decom-
posed after heating above 180◦C; IR (KBr) ν [cm−1] 3440, 2926, 2853, 1727, 1237, 1054;
1H NMR (CD3OD, 300 MHz) δ [ppm] 1.95–2.15 (m, 2H, H-1a, H-1b), 3.92 (s, 3H,
COOCH3), 4.22–4.34 (m, 1H, H-2), 4.46 (dd, J = 13.6 Hz, J = 7.8 Hz, 1H, H-3b), 4.76
(dd, J = 13.6 Hz, J = 2.8 Hz, 1H, H-3a), 8.51 (s, 1H, HC5 ); 13C NMR (CD3OD, 75.5
ꢁ
MHz) δ [ppm] 31.9 (d, J = 140.7 Hz, C-1), 52.3 (s, COOCH3), 57.2 (d, J = 17.8 Hz, C-3),
65.7 (d, J = 3.6 Hz, C-2), 129.8 (s, HC C), 139.5 (s, HC C), 162.1 (s, C O); 31P NMR
(CD3OD, 121.5 MHz) δ [ppm] 22.55; Anal. Calcd. for C7H12N3O6P×H2O: C, 29.69; H,
4.98; N, 14.84. Found: C, 29.36; H, 4.88; N, 14.68.
3-[4-(Benzoyloxymethyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonic
acid 8b. Compound 8b was obtained as a colorless oil (0.038 g, 93%); IR (film) ν [cm−1
]
1
3444, 2936, 2858, 1727, 1237, 1059, 765, 655; H NMR (CD3OD, 300 MHz) δ [ppm]
1.95–2.17 (m, 2H, H-1b, H-1a), 4.32–4.46 (m, 1H, H-2), 4.54 (dd, J = 13.8 Hz, J = 8.1
Hz, 1H, H-3b), 4.82 (dd, J = 13.8 Hz, J = 3.0 Hz, 1H, H-3a), 5.52 (s, 2H, CH2OC(O)Ph),
7.45–7.52 (m, 2H, Ar H), 7.59–7.70 (m, 1H, Ar H) 8.01–8.08 (m, 2H, Ar H), 8.44 (s,
1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 34.0 (d, J = 136.6 Hz, C-1), 57.9 (s,
ꢁ
CH2OC(O)Ph), 58.3 (d, J = 11.7 Hz, C-3), 67.0 (s, C-2), 129.5, 129.7, 130.6, 134.0 (s,
HC C), 134.6, 167.4 (s, C O); 31P NMR (CD3OD, 121.5 MHz) δ [ppm] 24.11; Anal.
Calcd. for C13H16N3O6P×2H2O: C, 41.38; H, 5.34; N, 11.14. Found: C, 41.52; H, 5.28;
N, 11.20.
2-Hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propylphosphonic
acid
8c.
Compound 8c was obtained as a colorless oil (0.042 g, 90%); IR (film) ν [cm−1] 3333,
1
2985, 2888, 1238, 1049, 965; H NMR (CD3OD, 300 MHz) δ [ppm] 2.05–2.27 (m, 2H,
H-1b, H-1a), 4.43–4.56 (m, 1H, H-2), 4.65 (dd, J = 13.8 Hz, J = 8.1 Hz, 1H, H-3b), 4.92
(dd, J = 13.8 Hz, J = 3.0 Hz, 1H, H-3a), 7.49–7.60 (m, 3H, Ar H), 7.82–7.87 (m, 2H,
Ar H), 8.88 (s, 1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 34.0 (d, J = 136.8 Hz,
ꢁ
C-1), 59.3 (d, J = 11.5 Hz, C-3), 66.9 (s, C-2), 126.2, 127.2, 127.5, 130.6, 131.5, 145.8;
31P NMR (CD3OD, 121.5 MHz) δ [ppm] 25.51; Anal. Calcd. for C11H14N3O4P×H2O: C,
43.86; H, 5.35; N, 13.95. Found: C, 44.03; H, 5.59; N, 14.08.
3-[4-(2-Fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonic acid
8d. Compound 8d was obtained as a colorless oil (0.040 g, 85%); IR (film) ν [cm−1] 3296,
1
2952, 2811, 1620, 1586, 1486, 1437, 1128, 1075, 976; H NMR (CD3OD, 300 MHz) δ
[ppm] 2.00–2.22 (m, 2H, H-1b, H-1a), 4.40–4.51 (m, 1H, H-2), 4.59 (dd, J = 13.7 Hz,
J = 8.1 Hz, 1H, H-3b), 4.85 (dd, J = 13.7 Hz, J = 3.2 Hz, 1H, H-3a), 7.25–7.33 (m,
2H, Ar H), 7.36–7.48 (m, 1H, Ar H), 8.00–8.08 (m, 1H, Ar H), 8.55 (d, J = 3.2 Hz,
1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 34.0 (d, J = 136.8 Hz, C-1), 58.3 (d,
ꢁ
J = 11.7 Hz, C-3), 67.0 (s, C-2), 117.3 (d, J = 22.8 Hz, C-3arom.), 117.4 (d, J = 15.3 Hz,
C-1arom.), 126.1 (d, J = 3.4 Hz, C-6arom.), 127.2 (d, J = 10.3 Hz), 128.9 (d, J = 2.9 Hz,
HC C), 132.2 (d, J = 8.3 Hz, C-4arom.), 140.7 (s, HC C), 160.6 (d, J = 249.2 Hz, C−F);
31P NMR (CD3OD, 121.5 MHz) δ [ppm] 26.81; Anal. Calcd. for C11H13FN3O4P×H2O:
C, 41.39; H, 4.74; N, 13.16. Found: C, 41.69; H, 4.93; N, 13.31.
3-[4-(3-Fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonic acid
8e. Compound 8e was obtained as a colorless oil (0.052 g, 83%); IR (film) ν [cm−1] 3306,
3086, 2955, 2814, 1621, 1584, 1487, 1436, 1127, 1075, 976; 1H NMR (CD3OD, 300 MHz)
δ [ppm] 2.05–2.21 (m, 2H, H-1b, H-1a), 4.41–4.51 (m, 1H, H-2), 4.57 (dd, J = 13.6 Hz,

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
445
J = 8.0 Hz, 1H, H-3b), 4.84 (dd, J = 13.6 Hz, J = 3.0 Hz, 1H, H-3a), 7.15–7.22 (m, 1H,
Ar H), 7.49–7.60 (m, 1H, Ar H), 7.61–7.78 (m, 2H, Ar H), 8.68 (s, 1H, HC5 ); 13C
ꢁ
NMR (CD3OD, 75.5 MHz) δ [ppm] 33.9 (d, J = 137.4 Hz, C-1), 58.8 (d, J = 12.1 Hz,
C-3), 66.9 (d, J = 1.5 Hz, C-2), 114.3 (d, J = 22.7 Hz, C-4arom.), 117.4 (d, J = 22.7 Hz,
C-2arom.), 123.1 (d, J = 7.6 Hz, C-6arom.), 125.9 (s, HC C), 130.7 (d, J = 7.6 Hz, Carom.),
132.4 (d, J = 15.1 Hz, Carom.), 145.4 (s, HC C), 164.5 (d, J = 249.2 Hz, C−F); 31P NMR
(CD3OD, 121.5 MHz) δ [ppm] 25.90; Anal. Calcd. for C11H13FN3O4P×H2O: C, 41.39; H,
4.74; N, 13.16. Found: C, 41.57; H, 4.86; N, 12.91.
3-[4-(2,4-Difluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonic
acid 8f. Compound 8f was obtained as a white solid (0.053 g, 95%); mp: 165−170◦C; IR
(KBr) ν [cm−1] 3333, 3071, 2924, 2853, 1638, 1590, 1510, 1079, 946; 1H NMR (CD3OD,
300 MHz) δ [ppm] 1.98–2.19 (m, 2H, H-1b, H-1a), 4.36–4.49 (m, 1H, H-2), 4.55 (dd, J =
13.8 Hz, J = 7.8 Hz, 1H, H-3b), 4.82 (dd, J = 13.8 Hz, J = 3.3 Hz, 1H, H-3a), 7.11–7.20
(m, 2H, Ar H), 8.08 (dt, J = 9.0 Hz, J = 6.3 Hz, 1H, Ar H-3), 8.48 (d, J = 3.3 Hz,
1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 33.8 (d, J = 137.4 Hz, C-1), 58.6 (d,
ꢁ
J = 12.3 Hz, C-3), 66.9 (s, C-2), 105.7 (t, J = 26.0 Hz, C-3arom.), 113.4 (dd, J = 22.3 Hz,
J = 3.4 Hz, Carom.), 127.2 (d, J = 9.7 Hz, Carom.), 130.5 (dd, J = 10.0 Hz, J = 4.6 Hz),
139.7 (s, HC C), 160.9 (dd, J = 251.6 Hz, J = 12.0 Hz C−F), 164.8 (d, J = 250.2
Hz, J = 12.0 Hz, C−F); 31P NMR (CD3OD, 121.5 MHz) δ [ppm] 24.50; Anal. Calcd.
for C11H12F2N3O4P×H2O: C, 39.18; H, 4.18; N, 12.46. Found: C, 38.89; H, 4.31; N,
12.58.
2-Hydroxy-3-[4-(pyridin-2-yl)-1,2,3-triazol-1-yl]propylphosphonic
acid
8g. Compound 8g was obtained as a colorless oil (0.044 g, 85%); IR (film) ν [cm−1] 3339,
2925, 2851, 1635, 1612, 1226, 1163, 1081, 997, 936, 787; 1H NMR (CD3OD, 300 MHz)
δ [ppm] 2.00–2.24 (m, 2H, H-1b, H-1a), 4.38–4.50 (m, 1H, H-2), 4.60 (dd, J = 13.8 Hz,
J = 7.8 Hz, 1H, H-3b), 4.87 (dd, J = 13.8 Hz, J = 3.0 Hz, 1H, H-3a), 8.03 (dt, J = 6.0
Hz, J = 0.9 Hz, 1H, Ar H), 8.54 (d, J = 8.2 Hz, 1H, Ar H), 8.70 (dt, J = 8.2 Hz, J
= 1.5 Hz, 1H, Ar H), 8.82 (d, J = 6.0 Hz, 1H, Ar H), 9.03 (s, 1H, HC5 ); 13C NMR
ꢁ
(CD3OD, 75.5 MHz) δ [ppm] 34.0 (d, J = 137.4 Hz, C-1), 57.8 (d, J = 11.3 Hz, C-3),
67.1 (s, C-2), 125.5, 126.8, 128.9, 139.8, 142.6, 144.7, 148.6; 31P NMR (CD3OD, 121.5
MHz) δ [ppm] 25.82; Anal. Calcd. for C10H13N4O4P×H2O: C, 39.74; H, 5.00; N, 18.54.
Found: C, 39.98; H, 4.81; N, 18.87.
2-Hydroxy-3-[4-(1-methyl-1H-imidazol-5-yl)-1,2,3-triazol-1-yl]propyl-
phosphonic acid 8h. Compound 8h was obtained as a colorless oil (0.035 g, 67%); IR
(film) ν [cm−1] 3427, 2923, 2854, 1639, 1449, 1165, 1057; 1H NMR (CD3OD, 300 MHz)
δ [ppm] 2.08 (ddd, J = 18.6 Hz, J = 15.3 Hz, J = 7.2 Hz, 1H, H-1b), 2.20 (ddd, J = 18.9
Hz, J = 15.3 Hz, J = 6.0 Hz, 1H, H-1a), 4.13 (s, 3H, CH3 N), 4.43 (ddddd, J = 14.4 Hz,
J = 7.8 Hz, J = 7.2 Hz, J = 6.0 Hz, J = 3.3 Hz, 1H, H-2), 4.57 (dd, J = 13.8 Hz, J =
7.8 Hz, 1H, H-3b), 4.80 (dd, J = 13.8 Hz, J = 3.3 Hz, 1H, H-3a), 7.92 (d, J = 1.8 Hz, 1H,
Himid), 8.60 (s, 1H, HC5 ), 9.11 (d, J = 1.8 Hz, 1H, Himid); 13C NMR (CD3OD, 75.5 MHz)
ꢁ
δ [ppm] 34.0 (d, J = 137.4 Hz, C-1), 36.5 (s, CH3 N), 57.6 (d, J = 11.7 Hz, C-3), 67.1 (s,
C-2), 119.2, 127.0, 127.6 (s, HC C), 135.1 (s, HC C), 137.9 (s, N CH N); 31P NMR
(CD3OD, 121.5 MHz) δ [ppm] 27.65. Anal. Calcd. for C9H14N5O4P×2H2O: C, 33.44; H,
5.61; N, 21.67. Found: C, 33.61; H, 5.49; N, 21.74.
3-(5-Amino-4-carbamoyl-1,2,3-triazol-1-yl)-2-hydroxypropylphosphonic
acid 8i. Compound 8i was obtained as a white powder (0.048 g, 95%), which decomposed
after heating above 180◦C; IR (KBr) ν [cm−1] 3321, 3199, 2926, 1638, 1543, 1259, 1130,
1
969; H NMR (CD3OD, 300 MHz) δ [ppm] 1.94–2.17 (m, 2H, H-1a, H-1b), 4.24 (dd,

446
I. E. GŁOWACKA ET AL.
J = 13.6 Hz, J = 6.8 Hz, H-3b), 4.35–4.82 (m, 2H, H-2, H-3a); 13C NMR (CD3OD,
75.5 MHz) δ [ppm] 32.7 (d, J = 136.7 Hz, C-1), 52.4 (d, J = 12.4 Hz, C-3), 66.3 (s, C-2),
121.5 (s, HC C), 146.5 (s, HC C), 165.6 (s, C O); 31P NMR (CD3OD, 121.5 MHz) δ
[ppm] 26.31; Anal. Calcd. for C6H12N5O5P×H2O: C, 25.45; H, 4.98; N, 24.73. Found: C,
25.61; H, 5.13; N, 24.58.
1-Hydroxy-2-[4-(methoxycarbonyl)-1,2,3-triazol-1-yl]ethylphosphonic
acid 9a. Compound 9a was obtained as a white solid (0.049 g, 92%); mp: 134–136◦C;
IR (KBr) ν [cm−1] 3345, 2969, 2924, 2851, 1727, 1251, 1224, 1085; 1H NMR (D2O, 300
MHz) δ [ppm] 3.88 (s, 3H, COOCH3), 4.26 (dt, J = 10.3 Hz, J = 3.0 Hz, 1H, H-1), 4.59
(ddd, J = 14.5 Hz, J = 10.3 Hz, J = 6.0 Hz, 1H, H-2a), 4.68–4.87 (m, 1H, H-2b), 8.54 (s,
1H, HC5 ); 13C NMR (D2O, 75.5 MHz) δ [ppm] 52.7 (s, COOCH3), 52.8 (s, C-2), 67.2 (d,
ꢁ
J = 158.6 Hz, C-1), 129.9 (s, HC C), 138.9 (s, HC C), 162.3 (s, C O); 31P NMR (D2O,
121.5 MHz) δ [ppm] 18.17; Anal. Calcd. for C6H10N3O6P: C, 28.70; H, 4.01; N, 16.73.
Found: C, 28.57; H, 3.97; N, 16.78.
2-[4-(Benzoyloxymethyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphosphonic
acid 9b. Compound 9b was obtained as a white powder (0.062 g, 77%), which
decomposed after heating above 170◦C; IR (KBr) ν [cm−1] 3028, 2982, 2890, 1720, 1258,
1
1020, 847, 720; H NMR (D2O, 300 MHz) δ [ppm] 4.20–4.40 (m, 1H, H-1), 4.52–4.72
(m, 1H, H-2b), 4.78–4.90 (m, 1H, H-2a), 5.48 (s, 2H, CH2OC(O)Ph), 7.47–7.58 (m, 2H,
Ar H), 7.60–7.66 (m, 1H, Ar H), 7.90–8.01 (m, 2H, Ar H), 8.23 (s, 1H, HC5 ); 13C
ꢁ
NMR (CD3OD, 75.5 MHz) δ [ppm] 51.8 (s, C-2), 58.4 (s, CH2OC(O)Ph), 68.3 (d, J =
160.6 Hz, C-1), 123.6 (s, HC C), 128.4, 129.0, 129.8 (Carom.), 133.3 (s, HC C), 139.2
(Cipso), 169.9 (s, C O); 31P NMR (D2O, 121.5 MHz) δ [ppm] 18.14; Anal. Calcd. for
C12H14N3O6P×H2O: C, 41.75; H, 4.67; N, 12.17. Found: C, 41.98; H, 4.75; N, 12.04.
1-Hydroxy-2-(4-phenyl-1,2,3-triazol-1-yl)ethylphosphonic acid 9c. Com-
pound 9c was obtained as a white powder (0.044 g, 80%); mp: 162–166◦C; IR (KBr)
1
ν [cm−1] 3074, 2989, 1225, 1015, 976, 765, 692; H NMR (D2O, 300 MHz) δ [ppm]
4.29 (dt, J = 10.3 Hz, J = 2.0 Hz, 1H, H-1), 4.60 (ddd, J = 14.8 Hz, J = 10.3 Hz,
J = 6.0 Hz, 1H, H-2a), 4.75–4.85 (m, 1H, H-2b), 7.39–7.59 (m, 3H, Ar H), 7.62–7.80
(m, 2H, Ar H), 8.41 (s, 1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 52.2 (d,
ꢁ
J = 10.7 Hz, C-2), 67.1 (d, J = 166.3 Hz, C-1), 121.8, 125.5, 128.1, 128.8 (Carom.), 130.4
(HC C), 147.0 (HC C); 31P NMR (D2O, 121.5 MHz) δ [ppm] 17.89; Anal. Calcd. for
C10H12N3O4P×H2O: C, 41.82; H, 4.91; N, 14.63. Found: C, 41.45; H, 5.02; N, 14.44.
2-[4-(2-Fluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphosphonic acid
9d. Compound 9d was obtained as a white solid (0.056 g, 86%); which decomposed
after heating above 180◦C; IR (KBr) ν [cm−1] 3231, 3012, 2989, 2909, 1487, 1210, 1048,
1
760; H NMR (D2O, 300 MHz) δ [ppm] 4.27 (dt, J = 10.7 Hz, J = 2.6 Hz, 1H, H-1),
4.53 (ddd, J = 13.9 Hz, J = 10.7 Hz, J = 5.7 Hz, 1H, H-2b), 4.75–4.87 (m, 1H H-2a),
7.11–7.21 (m, 2H, Ar H), 7.23–7.38 (m, 1H, Ar H), 7.79 (t, J = 7.5 Hz, 1H, Ar H),
8.30 (d, J = 2.4 Hz, 1H, HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 52.1 (d, J =
ꢁ
10.4 Hz, C-2), 67.4 (d, J = 165.4 Hz, C-1), 114.6 (d, J = 22.8 Hz, C-3arom.), 117.2 (d,
J = 12.4 Hz, C-1arom.), 122.6 (d, J = 3.0 Hz, C-5arom.), 123.8 (d, J = 12.4 Hz, Carom.),
126.4 (d, J = 3.0 Hz, HC C), 129.0 (d, J = 8.3 Hz, Carom.), 140.2 (s, HC C), 156.8 (d,
J = 246.0 Hz, F−Carom.); 31P NMR (D2O, 121.5 MHz) δ [ppm] 18.20. Anal. Calcd. for
C10H11FN3O4P×H2O: C, 39.35; H, 4.29; N, 13.77. Found: C, 39.52; H, 4.28; N, 13.89.
2-[4-(3-Fluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphosphonic acid
9e. Compound 9e was obtained as a white solid (0.058 g, 94%); mp: 172–175◦C; IR

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
447
1
(KBr) ν [cm−1] 3307, 3100, 2993, 1434, 1220, 1025, 777; H NMR (D2O, 300 MHz) δ
[ppm] 4.25 (dt, J = 10.3 Hz, J = 2.4 Hz, 1H, H-1), 4.56 (ddd, J = 13.8 Hz, J = 10.3 Hz,
J = 5.7 Hz, 1H, H-2b), 4.66–4.80 (m, 1H H-2a), 7.09 (t, J = 8.5 Hz, 1H, Ar H), 7.38–7.48
(m, 3H, Ar H), 8.29 (s, 1H, HC5 ); 13C NMR (D2O, 75.5 MHz) δ [ppm] 52.1 (d, J = 9.2
ꢁ
Hz, C-2), 65.0 (d, J = 155.2 Hz, C-1), 110.3 (d, J = 22.2 Hz, Carom.), 114.2 (d, J = 19.0
Hz, Carom.), 117.9 (d, J = 2.8 Hz, Carom.), 122.0 (s, HC C) 130.4 (d, J = 8.6 Hz, Carom.),
130.3 (d, J = 8.0 Hz, C-1arom.), 144.4 (s, C CH), 164.1 (d, J = 245.2 Hz, F Carom.); 31
P
NMR (D2O, 121.5 MHz) δ [ppm] 17.92. Anal. Calcd. for C10H11FN3O4P×H2O: C, 39.35;
H, 4.29; N, 13.77. Found: C, 39.15; H, 4.51; N, 13.88.
2-[4-(2,4-Difluorophenyl)-1,2,3-triazol-1-yl]-1-hydroxyethylphosphonic
acid 9f. Compound 9f was obtained as a white solid (0.065 g, 97%); mp: 194–198◦C; IR
1
(KBr) ν [cm−1] 3143, 2987, 2901, 1493, 1220, 1026, 979, 816; H NMR (CD3OD, 300
MHz) δ [ppm] 4.34 (dt, J = 10.2 Hz, J = 3.0 Hz, 1H, H-1), 4.71 (ddd, J = 14.1 Hz, J =
10.2 Hz, J = 6.0 Hz, 1H, H-2b), 4.95 (ddd, J = 14.1 Hz, J = 4.8 Hz, J = 3.0 Hz, 1H,
H-2a), 7.13–7.23 (m, 2H, Ar H), 8.06 (dt, J = 8.1 Hz, J = 6.3 Hz, 1H, Ar H), 8.60 (d,
J = 3.0 Hz, 1H, HC5 ); 13C NMR (DMSO-d6, 75.5 MHz) δ [ppm] 52.4 (d, J = 10.2 Hz,
ꢁ
C-2), 67.2 (d, J = 164.6 Hz, C-1), 104.0 (t, J = 25.8 Hz, C-3arom.), 112.4 (dd, J = 21.2 Hz,
J = 3.4 Hz, C-1arom.), 113.9 (dd, J = 13.0 Hz, J = 3.7 Hz, C-5arom.), 124.4 (d, J = 12.4
Hz, HC C), 128.4 (dd, J = 9.4 Hz, J = 5.2 Hz, C-6arom.), 140.4 (s, HC C), 159.3 (dd,
J = 254.2 Hz, J = 12.4 Hz, C-2arom.), 162.0 (dd, J = 252.5 Hz, J = 12.4 Hz, C-4arom.); 31
P
NMR (CD3OD, 121.5 MHz) δ [ppm] 19.43. Anal. Calcd. for C10H10F2N3O4P: C, 39.36;
H, 3.30; N, 13.77. Found: C, 39.33; H, 3.53; N, 13.62.
1-Hydroxy-2-[4-(pyridin-2-yl)-1,2,3-triazol-1-yl]ethylphosphonic acid 9g.
Compound 9g was obtained as a yellow pale powder (0.422 g, 94%), which decomposed
after heating above 180◦C; IR (KBr) ν [cm−1] 3154, 2980, 2930, 1602, 1222, 1023, 975,
1
786; H NMR (D2O, 300 MHz) δ [ppm] 4.23 (dt, J = 10.5 Hz, J = 2.7, 1H, H-1), 4.65
(ddd, J = 14.1 Hz, J = 10.5 Hz, J = 5.7 Hz, 1H, H-2b), 4.89 (ddd, J = 14.1 Hz, J = 7.5
Hz, J = 2.7 Hz, 1H, H-2a), 7.95 (t, J = 6.6 Hz, 1H, Ar H), 8.36 (d, J = 8.1 Hz, 1H,
Ar H), 8.60 (t, J = 8.1 Hz, 1H, Ar H), 8.70 (d, J = 6.6 Hz, 1H, Ar H), 8.85 (s, 1H,
HC5 ); 13C NMR (CD3OD, 75.5 MHz) δ [ppm] 50.4 (d, J = 10.4 Hz, C-2), 64.8 (d, J =
ꢁ
166.8 Hz C-1), 120.5 (s, Carom.), 122.6 (s, Carom.), 124.0 (HC C), 137.0 (s, Carom.), 147.0
(s, C CH), 148.4 (s, Carom.), 149.9 (s, Cipso); 31P NMR (D2O, 121.5 MHz) δ [ppm] 16.61.
Anal. Calcd. for C9H11N4O4P×1/2H2O: C, 38.72; H, 4.33; N, 20.07. Found: C, 38.53; H,
4.48; N, 19.92.
1-Hydroxy-2-[4-(1-methyl-1H-imidazol-5-yl)-1,2,3-triazol-1-yl]ethylpho-
sphonic acid 9h. Compound 9h was obtained as a white solid (0.042 g, 70%), which
decomposed after heating above 180◦C; IR (KBr) ν [cm−1] 3424, 3096, 2980, 2920, 2850,
1250, 1090, 1030, 976; 1H NMR (D2O, 300 MHz) δ [ppm] 3.91 (s, 3H, CH3 N), 4.29 (dt,
J = 10.3 Hz, J = 2.0 Hz, 1H, H-1), 4.59–4.69 (m, 1H, H-2a), 4.73–4.87 (m, 1H, H-2b),
7.70 (s, 1H, Himid), 8.42 (s, 1H, HC5 ), 8.77 (s, 1H, Himid); 13C NMR (D2O, 75.5 MHz) δ
ꢁ
[ppm] 35.1 (s, CH3 N), 52.3 (d, J = 10.6 Hz, C-2), 66.9 (d, J = 160.3 Hz C-1), 118.1,
125.1, 126.3 (s, HC C), 133.7 (s, HC C), 136.2 (s, N CH N); 31P NMR (D2O, 121.5
MHz) δ [ppm] 18.32. Anal. Calcd. for C8H12N5O4P×1/2H2O: C, 34.05; H, 4.64; N, 24.82.
Found: C, 34.03; H, 4.53; N, 24.67.
1-Hydroxy-2-(4,5-dimethoxycarbonyl-1,2,3-triazol-1-yl)ethylphosphonic
acid 9j. Compound 9j was obtained as a white solid (0.043 g, 91%); mp: 178–181◦C;
1
IR (KBr): ν [cm−1] 3238, 2954, 2910, 1730, 1220, 1024; H NMR (D2O, 300 MHz) δ

448
I. E. GŁOWACKA ET AL.
[ppm] 3.94 (s, 3H, COOCH3), 3.98 (s, 3H, COOCH3), 4.34 (dt, J = 10.1 Hz, J = 2.7 Hz,
1H, H-1), 4.78–5.01 (m, 2H, H-2a, H-2b); 13C NMR (D2O, 75.5 MHz) δ [ppm] 51.6 (d,
J = 13.5 Hz, C-2), 52.8 (s, COOCH3), 53.4 (s, COOCH3) 66.8 (d, J = 160.0 Hz, C-1),
131.7 (s, HC C), 139.0 (s, HC C), 159.9 (s, C O), 162.2 (s, C O); 31P NMR (D2O,
121.5 MHz) δ [ppm] 18.27; Anal. Calcd. for C8H12N3O8P: C, 31.08; H, 3.91; N, 13.59.
Found: C, 31.17; H, 3.77; N, 13.61.
REFERENCES
1. Aufort, M.; Herscovici, J.; Bouhours, P.; Moreau, N.; Girard, Ch. Bioorg. Med. Chem. 2008, 18,
1195–1198.
2. Demaray, J. A.; Thuener, J. E.; Dawson, M. N.; Sucheck, S. J. Bioorg. Med. Chem. 2008, 18,
4868–4871.
3. Castagnolo, D.; Radi, M.; Dessi, F.; Manetti, F.; Saddi, M.; Meleddu, R.; De Logu, A.; Botta, M.
Bioorg. Med. Chem. Lett. 2009, 19, 2203–2205.
4. Beena; Kumar, N.; Rohilla, R. K.; Roy, N.; Rawat, D. S. Bioorg. Med. Chem. Lett. 2009, 19,
1396–1398.
5. Chan, D. C. M.; Laughton, C. A.; Queener, S. F.; Stevens, M. F. G. Bioorg. Med. Chem. 2002,
10, 3001–3010.
6. Jordan, D. B.; Basarab, G. S.; Liao, D.-I.; Johnson, W. M. P.; Winzenberg, K. N.; Winkler, D. A.
J. Mol. Graphics Modell. 2001, 19, 434–447.
7. Aher, N. G.; Pore, V. S.; Mishra, N. N.; Kumar, A.; Shukla, P. K.; Sharma, A.; Bhat, M. K.
Bioorg. Med. Chem. Lett. 2009, 19, 759–763.
8. Kamal, A.; Shankaraiah, N.; Devaiah, V.; Reddy, K. L.; Juvekar, A.; Sen, S.; Kurian, N.; Zingde,
S. Bioorg. Med. Chem. 2008, 18, 1468–1473.
9. Chen, Y.; Lopez-Sanchez, M.; Savoy, D. N.; Billadeau, D. D.; Dow, G. S.; Kozikowski, A. P. J.
Med. Chem. 2008, 51, 3437–3448.
10. Cho, S.; Oh, S.; Um, Y.; Jung, J. H.; Ham, J.; Shin, W. S.; Lee, S. Bioorg. Med. Chem. Lett. 2009,
19, 382–385.
11. Zhou, L.; Amer, A.; Korn, M.; Burda, R.; Balzarini, J.; De Clercq, E.; Kern, E. R.; Torrence, P.
F. Antiviral Chem. Chemother. 2005, 16, 375–383.
12. Jorda˜o, A. K.; Afonso, P. P.; Ferreira, V. F.; De Souza, M. C. B. V.; Almeida, M. C. B.; Beltrame,
C. O.; Paiva, D. P.; Wardell, S. M. S. V.; Wardell, J. L.; Tiekink, E. R. T.; Damaso, C. R.; Cunha,
A. C. Eur. J. Med. Chem. 2009, 44, 3777–3783.
13. Lazrek, H. B.; Taourirte, M.; Oulih, T.; Barascut, J. L.; Imbach, J. L.; Pannecouque, C.; Witrouw,
M.; De Clercq, E. Nucleosides, Nucleotides Nucleic Acids 2001, 20, 1949–1960.
14. Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore, M. R.; Cascieri, M. A.; Colwell, L. F.
Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.;
Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 2000, 10, 2111–2114.
15. Sternfeld, F.; Carling, R. W.; Jelley, R. A.; Ladduwahetty, T.; Merchant, K. J.; Moore, K. W.
Reeve, A. J.; Street, L. J.; O’Connor, D.; Wafford, K.; Tattersall, F. D.; Collinson, N.; Dawson,
G. R.; Castro, J. L.; MacLeod, A. M. J. Med. Chem. 2004, 47, 2176–2179.
16. Ryu, E. H.; Zhao, Y. Org. Lett. 2005, 7, 1035–1037.
17. Chittaboina, S.; Xie, F.; Wang, Q. Tetrahedron Lett. 2005, 46, 2331–2336.
18. Zhu, X.; Schmidt, R. R. J. Org. Chem. 2004, 69, 1081–1085.
19. Kuijpers, B. H. M.; Groothuys, S.; Keereweer, A. R.; Quaedflieg, P. J. L. M.; Blaauw, R. H.; van
Delft, F. L.; Rutjes, F. P. J. T. Org. Lett. 2004, 6, 3123–3126.
20. Dondoni, A.; Giovannini, P. P.; Massi, A. Org. Lett. 2004, 6, 2929–2932.
21. Tornøe, C.W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064.
22. Punna, S.; Kuzelka, J.; Wang, Q.; Finn, M. G. Angew. Chem., Int. Ed. 2005, 44, 2215–2220.

1-HYDROXY-2-(1,2,3-TRIAZOL-1-YL)ETHYLPHOSPHONATES
449
23. Mocharla, V. P.; Colasson, B.; Lee, L. V.; Ro¨per, S.; Sharpless, K. B.; Wong, C. H.; Kolb, H. C.
Angew. Chem., Int. Ed. 2005, 44, 116–120.
24. Manetsch, R.; Krasin´ski, A.; Radic´, Z.; Raushel, J.; Taylor, P.; Sharpless, K. B.; Kolb, H. C. J.
Am. Chem. Soc. 2004, 126, 12809–12818.
25. Weller, R. L.; Rajski, S. R. Org. Lett. 2005, 7, 2141–2144.
26. Suarez, P. L.; Ga´ndara, Z.; Go´mez, G.; Fall, Y. Tetrahedron Lett. 2004, 45, 4619–4621.
27. Suh, B. C.; Jeon, H. B.; Posner, G. H.; Silverman, S. M. Tetrahedron Lett. 2004, 45, 4623–4625.
28. Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.; Pyun, J.; Fre´chet,
J. M. J.; Sharpless, K. B.; Fokin, V.V. Angew. Chem., Int. Ed. 2004, 43, 3928–3932.
29. Ornelas, C.; Aranzaes, J. R.; Cloutet, E.; Alves, S.; Astruc, D. Angew. Chem., Int. Ed. 2007, 46,
872–877.
30. Al-Masoudi, N. A.; Al-Soud, Y. A.; Abdul-Zahra, A. Heteroat. Chem. 2004, 15, 380–387.
31. Sallam, M. A. E.; Louis, F. F. Chirality 2004, 16, 331–335.
32. Hilderbrand, R. L. The Role of Phosphonates in Living Systems; CRC Press: Boca Raton, FL,
1983.
33. Artyushin, O. I.; Vorob’eva, D. V.; Vasil’ev,a T. P.; Osipov, S. N.; Ro¨schenthaler, G.-V.; Odinets,
I. L. Heteroat. Chem. 2008, 19, 293–300.
34. Journet, M.; Cai, D.; Kowal, J. J.; Larsen, R. D. Tetrahedron Lett. 2001, 42, 9117–9118.
35. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. 2002, 41, 2596–2599.
36. Norris, P.; Horton, D.; Levine, B. R. Heterocycles 1996, 43, 2643–2655.
37. Talekar, R. R.; Wightman, R. H. Tetrahedron 1997, 53, 3831–3842.
38. Griffin, E.; Kundu, S. K. J. Org. Chem. 1969, 34, 1532–1539.
39. Rico, I.; Bou, A.; Lalo, J.; Maffrand, J. P.; Frehel, D. New. J. Chem. 1989, 13, 507–510.
40. Zygmunt, J.; Walkowiak, U.; Mastalerz, P. Pol. J. Chem. 1980, 54, 233–240.
41. Głowacka, I. E. Tetrahedron: Asymmetry 2009, 20, 2270–2278.
42. Shi, J.; Liu, L.; He, J.; Meng, X.; Guo, Q. Chem. Lett. 2007, 36, 1142–1143.
43. Saito, Y.; Escuret, V.; Durantel, D.; Zoulim, F.; Schinazi, R. F.; Agrofoglio, L. A. Bioorg. Med.
Chem. 2003, 11, 3633–3639.
44. Palacios, F.; Ochoa de Retana, A. M.; Pagalday, J. Heterocycles 1994, 38, 95–102.