Synthesis of (Tetrahydrofuranyl)methyl-1,2,3-triazoles through alkyne-azide cycloaddition catalyzed by a dithioic acid copper(I) complex

Article abstract of DOI:10.1080/00397911.2010.516052

(Tetrahydrofuranyl)methyl-1,2,3-triazoles were synthesized from tetrahydrofurfuryl tosylate and several alkynes in the presence of catalytic amounts of a 3-hydroxy-3-phenyl-2-propenendithioate-bis(triphenylphosphine) copper(I) complex. The reaction proces

Full text of DOI:10.1080/00397911.2010.516052

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Synthesis of
(Tetrahydrofuranyl)methyl-1,2,3-
triazoles Through Alkyne–Azide
Cycloaddition Catalyzed by a Dithioic
Acid Copper(I) Complex
Bayardo E. Velasco a , Aydeé Fuentes a , Carlos Gonzalez a , David
Corona a , Iván García-Orozco a & Erick Cuevas-Yañez a
a Centro Conjunto de Investigación en Química Sustentable UAEM-
UNAM, Toluca, México
Version of record first published: 11 Jul 2011.
To cite this article: Bayardo E. Velasco , Aydeé Fuentes , Carlos Gonzalez , David Corona , Iván
García-Orozco & Erick Cuevas-Yañez (2011): Synthesis of (Tetrahydrofuranyl)methyl-1,2,3-triazoles
Through Alkyne–Azide Cycloaddition Catalyzed by a Dithioic Acid Copper(I) Complex, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:20, 2966-2973
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Synthetic Communications1, 41: 2966–2973, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516052
SYNTHESIS OF (TETRAHYDROFURANYL)METHYL-
1,2,3-TRIAZOLES THROUGH ALKYNE–AZIDE
CYCLOADDITION CATALYZED BY A DITHIOIC ACID
COPPER(I) COMPLEX
´
Bayardo E. Velasco, Aydee Fuentes, Carlos Gonzalez,
David Corona, Ivan Garcıa-Orozco, and Erick Cuevas-Yanez
´
´
˜
´
Centro Conjunto de Investigacion en Quımica Sustentable
UAEM-UNAM, Toluca, Mexico
´
´
GRAPHICAL ABSTRACT
Abstract (Tetrahydrofuranyl)methyl-1,2,3-triazoles were synthesized from tetrahydro-
furfuryl tosylate and several alkynes in the presence of catalytic amounts of a 3-hydroxy-
3-phenyl-2-propenendithioate-bis(triphenylphosphine) copper(I) complex. The reaction
process is carried in out under mild conditions, and bases or reducing agents were not used.
The reaction afforded the 1,4-regioisomers in excellent yields.
Keywords Alkyne; azide; dithioic acid copper complex; 1,2,3-triazole
INTRODUCTION
Research in novel compounds with antiviral and anticancer properties is
highly required by society at these times. In this context, the copper-catalyzed
alkyne–azide cycloaddition (CuAAC, a ‘‘click’’ reaction) provides a powerful tool
to synthesize new compounds and to create novel libraries that support investiga-
tions against cancer and other diseases.[1] Thus, many groups have reported efficient
syntheses of nucleotide=nucleoside analogs that have been tested as potent antiviral
precursors.[2]
Motivated by the preceding reports, we decided to study the catalytic activity
of a novel kind of dithioic acid copper(I) complexes,[3] with the aim of synthesizing
1,2,3-triazoles through CuAAC[4] and emphasizing preparation of compounds
with potential antiviral activity. Herein is a summary of our recent endeavors in
this area.
Received May 6, 2010.
Address correspondence to Erick Cuevas-Yan˜ez, Centro Conjunto de Investigacion en Quımica
´
Sustentable UAEM-UNAM, Carretera Toluca Atlacomulco Km 14.5, Toluca, C.P. 50200, Mexico.
´
´
E-mail: ecuevasy@uaemex.mx
2966

(TETRAHYDROFURANYL)METHYL-1,2,3-TRIAZOLES
2967
In our initial studies, tetrahydrofurfuryl tosylate 2 was obtained from commer-
cially available tetrahydrofurfuryl alcohol 1. Reactions on tosylate 2 under various
conditions failed to provide the corresponding azide. In contrast, one-pot formation
of triazole 4 was possible from successive treatment of tosylate 2 with sodium azide
and phenylacetylene using catalytic amounts of 3-hydroxy-3-phenyl-2-propenen-
dithioate-bis(triphenylphosphine)copper(I) complex 3 (Scheme 1). A similar one-step
process was previously described by Feldman and coworkers,[5] and in our case, this
procedure immediately showed promise.
After some experimentation, the protocol described in the experimental part
was particularly effective for the generation of 4. In the same way, several alkynes
were readily reacted under similar conditions with tosylate 2 to afford the corre-
sponding 1,2,3-triazoles (Table 1, entries 1–11). The noteworthy features of this pro-
cess are its generality and the economy in the use of reagents and catalyst, because
the process requires only 0.4% mol catalyst=alkyne. Moreover, the reaction was car-
ried out at room temperature (10 h) or at 60 ꢀC (2 h) without loss of efficiency. Other
catalytic systems were tested, such as CuSO4–sodium ascorbate in tBuOH–water[6]
and CuI–diisopropylethyl amine (DIPEA).[7] However, catalysis using CuSO4–
sodium ascorbate failed in our case, and poor yields were obtained when CuI–
DIPEA was used as catalytic system. Therefore, dithioic acid copper(I) complex 3
might be a simple, useful, and effective catalyst to obtain 1,2,3-triazoles in good
yields and good purity levels.
In addition, tetrahydrofurfuryl alcohol 1 was alkylated with propargyl bromide
to give the alkyne 5, which was treated with benzyl azide in the presence of catalytic
amounts of dithioic acid copper(I) complex 3 (Scheme 2). Thus, alcohol 1 represents
an alternative source of alkynes in this kind of process.
In conclusion, (tetrahydrofuranyl)methyl-1,2,3-triazoles were easily obtained
when tetrahydrofurfuryl tosylate 2 was treated with diverse terminal alkynes using
3-hydroxy-3-phenyl-2-propenendithioate-bis(triphenylphosphine)copper(I) complex
3 as catalyst. This process occurs in one step, and additional bases or reducing agents
are not required. The simplicity of the method suggests that this route to 1,2,3-
triazoles will enjoy widespread application.
Scheme 1. One-pot synthesis of triazole 4 from tosylate 2 using catalyst 3.

2968
B. E. VELASCO ET AL.
Table 1. Synthesis of 1,2,3-triazoles from tosylate 2 using catalyst 3
Entry
1
Alkyne
1,2,3-Triazol
Yield (%)
100 (85)a
2
3
93 (65)
97 (77)
4
5
6
96 (86)
97 (72)
99 (85)
7
74 (54)
8
9
50 (34)
84 (73)
10
88 (53)
(Continued )

(TETRAHYDROFURANYL)METHYL-1,2,3-TRIAZOLES
2969
Table 1. Continued
Entry
11
Alkyne
1,2,3-Triazol
Yield (%)
50 (31)
Note. Crude yields were determined by HPLC.
aYields in parentheses were determined after purification.
Scheme 2. Synthesis of triazole 6 from alkyne 5 using catalyst 3.
EXPERIMENTAL
The starting materials were purchased from Aldrich Chemical Co. and were
used without further purification. Solvents were distilled before use. Silica plates
0.20 mm thickness were used for thin-layer chromatography (TLC). Melting points
were determined with a Fisher-Johns melting-point apparatus and are uncorrected.
1H and 13C NMR spectra were recorded using a Varian 500 instrument, and the
chemical shifts (d) are given in parts per million (ppm) relative to tetramethylsilane
(TMS) as internal standard (0.00). For analytical purposes, the mass spectra
were recorded on a Bruker MicroTOF II in the electrospray ionization (ESI) mode,
via direct inlet probe. Infrared (IR) spectra were recorded on a Nicolet Magna 55-X
Fourier transform (FT) instrument.
Synthesis of Tetrahydrofurfuryl Tosylate (2)
Pyridine (9.7 g, 122.6 mmol) to a vigorously stirring suspension of tetrahydro-
furfuryl alcohol (10.0 g, 97.9 mmol) and p-toluensulfonyl chloride (23.3 g,
122.2 mmol) in 1,2-dichloroethane (40 mL) was added dropwise, maintaining the
temperature between 30 and 35 ꢀC. The resulting mixture was stirred at 60 ꢀC for
4 h. A solution of Na2CO3 (6.25 g, 58.9 mmol) in water (20 ml) was added, and the
organic layer was separated and washed with water (20 ml). The aqueous phase

2970
B. E. VELASCO ET AL.
was extracted with CH2Cl2 (3 ꢁ 50 mL). The organic extracts were joined and dried
over Na2SO4, and the solvent was removed in vacuo to yield a crude yellow oil, which
crystallized with the time as slightly yellow needles (17.2 g, 69%), mp 25 ꢀC. IR
1
(ATR, cmꢂ1) 2953, 2873, 1599, 1355, 1174. H NMR (500 MHz, CDCl3) d 1.60
(m, 1H), 1.81–1.99 (m, 3H), 2.24 (s, 3H), 3.9 (m, 2H), 3.95 (m, 2H), 4.05 (m, 1H),
7.31 (d, 2H, J ¼ 8 Hz), 7.78 (d, 2H, J ¼ 8 Hz). 13C NMR (125 MHz, CDCl3) d
21.5, 25.5, 27.7, 68.5, 71.7, 75.8, 127.8, 129.8, 132.8, 144.8. HRESIMS calculated
for [C5H10O2 þNa]þ: 125.0578; found: 125.0579.
Synthesis of (Tetrahydrofuranyl)methyl-1,2,3-triazoles: Typical
Procedure
Tosylate 2 (5.0 g, 19.5 mmol) was added to a solution of sodium azide (1.9 g,
29 mmol) in dimethylformamide (DMF) (10 ml) and water (0.3 mL). The resulting
mixture was stirred at 80 ꢀC for 4 h. A solution of phenylacetylene (2.1 mL, 1.96 g,
19.3 mmol) and catalyst 3 (0.075 g, 0.097 mmol) in methanol (30 mL) was added,
and the resulting mixture was stirred at 60 ꢀC for 2 h or at room temperature for
10 h. The reaction was quenched in water (50 ml) and extracted with toluene
(40 ml ꢁ 2). The combined organic extracts were dried over Na2SO4 and treated with
activated charcoal (0.5 g). The mixture was filtered and evaporated in vacuo, and the
product was crystallized from hot ethyl acetate and n-heptane (toluene and pet-
roleum spirits were also used, depending of product solubility).
4-Phenyl-1-(tetrahydrofuran-2-ylmethyl)-1H-[1,2,3]triazole (Entry 1)
1
White solid (100%), mp 74 ꢀC. IR (ATR, cmꢂ1) 2803, 2732, 1500. H NMR
(500 MHz, CDCl3) d 1.58 (m, 1H), 1.68–1.77 (m, 1H), 1.83 (m, 1H), 2.01 (m, 1H),
4.74 (m, 2H), 4.22 (m, 1H), 4.36 (m, 1H), 4.54 (d, 2H), 7.27 (m, 1H), 7.38 (m,
2H), 7.82 (m, 2H), 7.93 (s, 1H). 13C NMR (125 MHz, CDCl3) d 25.6, 28.4, 53.8,
68.5, 77.2, 120.9, 125.68, 127.9, 128.7, 130.78, 147.6. HRESIMS calculated for
[C13H15N3O þNa]þ: 252.1113; found: 252.1249.
1-(Tetrahydrofuran-2-ylmethyl)-4-p-tolyloxymethyl-1H-
[1,2,3]triazole (Entry 2)
1
White solid (93%), mp 57 ꢀC. IR (ATR, cmꢂ1) 2857, 1857, 1598, 1500. H
NMR (500 MHz, CDCl3) d 1.54 (m, 1H), 1.56 (m, 1H), 1.66 (m, 1H), 1.68 (m,
1H), 1.81 (m, 1H), 2.27 (s, 3H), 3.71 (m, 2H), 4.19 (m, 1H), 4.23 (m, 1H), 4.49
(m, 1H), 5.20 (s, 2H), 7.26 (d, 2H,), 7.75 (s, 1H), 7.86 (d, 2H). 13C NMR
(125 MHz, CDCl3) d 20.4, 25.6, 28.4, 53.836 (NCH2), 62.165 (OCH2), 77.128
(OCH), 114.7, 123.9, 129.9, 130.3, 144.3, 156.1. HRESIMS calculated for
[C15H19N3O2 þ Na]þ: 296.1375; found: 296.1457.
4-(4-Chloro-phenoxymethyl)-1-(tetrahydrofuran-2-ylmethyl)-1H-
[1,2,3]triazole (Entry 3)
1
White solid (97%), mp 83 ꢀC. IR (ATR, cmꢂ1) 2928, 2857, 1875, 1491. H
NMR (500 MHz, CDCl3) d 1.83–1.87 (m, 1H), 2.03 (m, 1H), 3.74 (m, 2H), 4.22

(TETRAHYDROFURANYL)METHYL-1,2,3-TRIAZOLES
2971
(m, 1H), 4.34 (m, 1H), 4.52 (m, 1H), 5.18 (s, 2H), 6.92 (d, 2H), 7.23 (d, 2H), 7.66 (s,
1H). 13C NMR (125 MHz, CDCl3) d 25.6, 28.4, 53.9, 62.3, 68.5, 77.1, 116.2, 124.0,
126.0, 129.3, 143.6, 156.8. HRESIMS calculated for [C14H16ClN3O2 þ Na]þ:
316.0829; found: 316.0914.
4-(4-Bromo-phenoxymethyl)-1-(tetrahydrofuran-2-ylmethyl)-1H-
[1,2,3]triazole (Entry 4)
1
White solid (96%), mp 86 ꢀC. IR (ATR, cmꢂ1) 2947, 2883, 1585, 1500. H
NMR (500 MHz, CDCl3) d 1.53 (m, 1H), 1.66 (m, 1H), 1.80 (m, 1H), 2.00 (m,
1H), 3.71 (m, 2H), 4.21 (m, 1H), 4.33 (m, 1H), 4.51 (m, 1H), 5.16 (s, 2H), 6.87 (d,
2H, J ¼ 8.5 Hz), 7.36 (d, 2H, J ¼ 8.5 Hz), 7.77 (s, 1H). 13C NMR (125 MHz, CDCl3)
d 25.6, 28.4, 53.8, 62.1, 68.5, 77.0, 113.3, 116.7, 124.0, 132.2, 143.5, 157.3. HRESIMS
calculated for [C14H16BrN3O2 þ Na]þ: 360.0324; found: 360.0397.
4-[1-(Tetrahydrofuran-2-ylmethyl)-1H-[1,2,3]triazol-4-ylmethoxy]-
benzaldehyde (Entry 5)
1
White solid (97%), mp 82 ꢀC. IR (ATR, cmꢂ1) 2850, 2750, 1652, 1589. H
NMR (500 MHz, CDCl3) d 1.58 (m, 1H), 1.70 (m, 1H), 1.84 (m, 1H), 2.04 (m,
1H), 3.74 (m, 2H), 4.23 (m, 1H), 4.35 (m, 1H), 4.54 (m, 1H), 5.30 (s, 2H), 7.10 (d,
2H, J ¼ 8 Hz), 7.28 (d, 2H, J ¼ 8 Hz), 7.836 (s, 1H), 9.980 (s, 1H). 13C NMR
(125 MHz, CDCl3) d 25.6, 28.5, 53.9, 62.1, 68.582, 77.1, 115.1, 124.2, 130.3, 131.9,
143.0, 163.2, 190.7. HRESIMS calculated for [C15H17N3O3 þ Na]þ: 310.1168; found:
310.1188.
4-[1-(Tetrahydrofuran-2-ylmethyl)-1H-[1,2,3]triazol-4-ylmethoxy]-
benzoic Acid Methyl Ester (Entry 6)
1
White solid (99%), mp 96 ꢀC. IR (ATR, cmꢂ1) 2803, 2732, 1678. H NMR
(500 MHz, CDCl3) d 1.55 (m, 1H), 1.67 (m, 1H), 1.83 (m, 1H), 2.01 (m, 1H), 3.72
(m, 2H), 3.87 (s, 3H), 4.20 (m, 1H), 4.35 (m, 1H), 4.53 (m, 1H), 5.26 (s, 2H), 7.00
(d, 2H, J ¼ 9 Hz), 7.79 (s, 1H), 7.98 (d, 2H, J ¼ 9 Hz). 13C NMR (125 MHz, CDCl3)
d 25.6, 28.5, 51.8, 53.9, 62.0, 68.5, 77.1, 114.4, 123.0, 124.1, 131.5, 143.3, 161.3, 166.7.
HRESIMS calculated for [C16H19N3O4 þNa]þ: 340.1273; found: 340.1357.
4-(4-Methoxyphenoxymethyl)-1-(tetrahydrofuran-2-ylmethyl)-1H-
[1,2,3]triazole (Entry 7)
1
White solid (74%), mp 71 ꢀC. IR (ATR, cmꢂ1): 2803, 2732, 1500. H NMR
(500 MHz, CDCl3) d 1.56 (m, 1H), 1.68 (m, 1H), 1.82 (m, 1H), 2.00 (m, 1H), 3.73
(s, 3H), 3.75 (s, 2H), 4.20 (m, 1H), 4.20 (m, 1H), 4.32 (m, 1H), 4.48 (m, 1H), 5.14
(s, 2H), 6.80 (d, 2H, J ¼ 8 Hz), 6.90 (d, 2H, J ¼ 8 Hz), 7.75 (s, 1H). 13C NMR
(125 MHz, CDCl3) d 25.5, 28.4, 53.7, 55.6, 62.6, 68.4, 77.0, 114.5, 115.8, 123.9,
144.1, 152.3, 154.091. HRESIMS calculated for [C15H19N3O3 þ Na]þ: 312.1324;
found: 312.1398.

2972
B. E. VELASCO ET AL.
3-[1-(Tetrahydrofuran-2-ylmethyl)-1H-[1,2,3]triazol-4-yl]-propan-1-ol
(Entry 8)
Colorless oil (50%). IR (ATR, cmꢂ1) 3354, 2937, 2854, 1542. 1H NMR
(500 MHz, CDCl3) d 1.56 (m, 1H), 1.70 (m, 1H), 1.83 (m, 3H), 2.02 (m, 1H), 2.82
(t, 2H), 3.59 (s, 1H), 3.68 (t, 2H), 3.74 (m, 2H), 4.20 (m, 1H), 4.31 (m, 1H), 4.5
(d, 1H), 7.51 (s, 1H). 13C NMR (125 MHz, CDCl3) d 21.9, 25.5, 28.48, 32.0, 53.6,
61.4, 68.4, 77.2, 122.1, 147.4. HRESIMS calculated for [C10H17N3O3 þ Na]þ:
234.1218; found: 234.1325.
Butyl-carbamic Acid 1-(Tetrahydrofuran-2-ylmethyl)-1H-
[1,2,3]triazol-4-ylmethyl Ester (Entry 9)
1
White solid (84%), mp 88 ꢀC. IR (ATR, cmꢂ1) 2946, 2857, 1705, 1527. H
NMR (500 MHz, CDCl3) d 0.91 (t, 3H), 1.32 (m, 2H), 1.60 (m, 1H), 1.74 (m, 1H),
1.87 (m, 1H), 2.03 (m, 1H), 3.17 (t, 2H), 3.76 (m, 2H), 4.23 (m, 1H), 4.34 (m, 1H),
4.50 (m, 1H), 5.00 (s, 1H), 5.18 (s, 2H), 7.785 (s, 1H). 13C NMR (125 MHz, CDCl3)
d 13.701 (CH3), 19.868 (CH2), 25.654 (CH2), 28.564 (CH2), 31.988 (CH2), 40.788
(NHCH2), 53.859 (OCH2), 57.8, 68.5, 77.1, 124.8, 143.4, 153.2. HRESIMS calcu-
lated for [C13H22N4O3 þ Na]þ: 305.1590; found: 305.1676.
4-[5-Chloro-2-(2,4-dichloro-phenoxy)-phenoxymethyl]-
1-(tetrahydro-furan-2-ylmethyl)-1H-[1,2,3]triazole (Entry 10)
1
White solid (88%), mp 86ꢀC. IR (ATR, cmꢂ1) 2947, 2883, 1500. H NMR
(500MHz, CDCl3) d 1.53 (m, 1H), 1.64 (m, 1H), 1.82 (m, 1H), 1.98 (m, 1H), 3.73 (t,
2H), 4.18 (m, 1H), 4.31 (m, 1H), 4.47 (m, 1H), 5.19 (s, 2H), 6.65 (m, 1H), 6.92 (m,
2H), 7.08 (dd, 1H, J ¼ 2.5Hz) 7.15 (d, 1H, J ¼ 1.5 Hz), 7.41 (d, 1H, J ¼ 2.5 Hz), 7.513
(s, 2H). 13C NMR (125MHz, CDCl3) d 24.6, 27.4, 52.8, 62.4, 67.5, 75.9, 114.9,
117.1, 117.2, 120.8, 122.9, 123.3, 126.7, 126.9, 129.3, 129.5, 142.1, 142.3, 148.9, 151.1.
HRESIMS calculated for [C20H18Cl3N3O3 þ Na]þ: 476.0311; found: 476.0423.
4-(Tetrahydrofuran-2-ylmethoxymethyl)-1-(tetrahydrofuran-2-
ylmethyl)-1H-[1,2,3]triazole (Entry 11)
1
Colorless oil (50%). IR (ATR, cmꢂ1) 2949, 2885, 1500. H NMR (500 MHz,
CDCl3) d 1.568–2.064 (m, 8H), 3.49 (m, 2H), 3.70 (m, 2H), 3.78 (m, 2H), 4.02 (m,
1H), 4.21 (m, 1H), 4.34 (m, 1H), 4.49 (m, 1H), 4.64 (m, 2H), 7.78 (s, 1H). 13C
NMR (125 MHz, CDCl3) d 25.3, 27.7, 28.2, 28.3, 53.4, 64.4, 67.8, 68.0, 72.6, 76.8,
77.8, 131.6, 144.5. HRESIMS calculated for [C13H21N3O3 þ Na]þ: 290.1481; found:
290.1537.
Synthesis of Triazole 6
Tetrahydrofurfuryl alcohol (2.9 g, 75.6 mmol) to a vigorously stirring suspension
of 60% NaH (7.0 g, 68.5 mmol) in THF (40 mL), was added dropwise maintaining the
temperature below 30 ꢀC. The resulting mixture was stirred at 30 ꢀC for 0.5 h. Propar-
gyl bromide (12. 2 g, 101.7 mmol) was added dropwise, maintaining the temperature

(TETRAHYDROFURANYL)METHYL-1,2,3-TRIAZOLES
2973
between 30 and 40 ꢀC. The resulting mixture was stirred at 40 ꢀC for 4 h. The mixture
was filtered and evaporated in vacuo, and the crude product 5 (73%) was used without
purification in the next step. Benzyl azide (1.1 g, 8.2 mmol), alkyne 5 (1.2 g, 8.2 mmol),
and catalyst 3 (32 mg, 0.04 mmol) in CH3CN (30 mL) were stirred at 60 ꢀC for 13 h.
The solvent was evaporated in vacuo, and charcoal (0.5 g) and toluene (25 mL) were
added. The resulting mixture was stirred for 0.5 h, and the solvent was evaporated
in vacuo. The product was purified by column chromatography (SiO2, CH2Cl2) to
afford a red oil (2.2 g, 88%). Spectral data for compound 6: IR (ATR, cmꢂ1) 2947,
1
2883, 1500. H NMR (500 MHz, CDCl3) d 1.17 (m, 1H), 1.73 (m, 3H), 3.37 (m,
2H), 3.61 (m, 1H), 3.71 (m, 1H), 3.93 (m, 1H), 4.57 (s, 2H), 5.04 (s, 2H), 7.16 (d,
2H), 7.23 (m, 3H,), 7.42 (s, 1H). 13C NMR (125 MHz, CDCl3) 24.5, 26.9, 53.0, 63.8,
67.2, 72.1, 76.7, 121.5, 127.0, 127.1, 127.5, 127.9, 128.0, 133.6, 144.5. HRESIMS cal-
culated for [C15H19N3O2 þ Na]þ: 296.1375; found: 296.1379.
ACKNOWLEDGMENTS
Financial support from CONACYT (No. 84390) is gratefully acknowledged.
´
The authors would like to thank OrganoSıntesis, S. A. de C. V., for some graciously
donated solvents and reagents, and M. C. Nieves Zavala (IQ-UNAM) for the
technical support.
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