Microwave-mediated cycloaddition of azides to propargylic ethers in PEG-200

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Microwave-Mediated Cycloaddition of
Azides to Propargylic Ethers in PEG-200
Hulluru Surya Prakash Rao a & Guravaiah Chakibanda a
a Department of Chemistry , Pondicherry University , Puducherry ,
605 014 , India
Published online: 16 May 2013.
To cite this article: Hulluru Surya Prakash Rao & Guravaiah Chakibanda (2013) Microwave-
Mediated Cycloaddition of Azides to Propargylic Ethers in PEG-200, Organic Preparations
and Procedures International: The New Journal for Organic Synthesis, 45:3, 232-240, DOI:
10.1080/00304948.2013.786575
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Organic Preparations and Procedures International, 45:232–240, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2013.786575
Microwave-Mediated Cycloaddition of Azides
to Propargylic Ethers in PEG-200
Hulluru Surya Prakash Rao and Guravaiah Chakibanda
Department of Chemistry, Pondicherry University, Puducherry 605 014, India
The copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) is the most celebrated click
reaction owing to several desirable features such as atom economy, high yields, terminal
alkyne chemo-selectivity, regio-selectivity in azide addition, true catalytic power of the
Cu(I) species, tolerance to plethora of functional groups and reaction conditions. (Scheme
1).1,2 The reaction is generally conducted with catalytic amount of inexpensive and readily
available copper(II) sulfate and sodium ascorbate.3,4 Sodium ascorbate acts as the reducing
agent to generate reactive Cu(I) species within the reaction medium.
Scheme 1
Even though several improvements in the reaction conditions such as variations in the
copper(I) species,5,6 microwave heating,7–9 acid additives10 have been introduced, there is
still room for fine tuning to improve efficiency particularly with respect to the solvent used. It
occurred to us that polyethylene glycol-200 (PEG-200), an environmentally benign solvent,
could be employed as the solvent in CuAAC particularly when conducted under microwave
irradiation.11 PEG-200 is a water soluble, bio-compatible liquid which efficiently absorbs
microwave radiation of 2.45 GHz, the frequency used in microwave synthesizers. PEG-
200 is practically insoluble in non-polar solvents such as tert-butyl methyl ether and
this property can be used for the recovery of many organic compounds from solutions,
thus leaving behind the solvent and the inorganic catalysts.12 Herein we describe optimal
conditions for CuAAC reaction of azides with propargylic ethers towards facile synthesis
of several triazole-natural product conjugates.
Received October 9, 2012; in final form february 12, 2013.
Address correspondence to Hulluru Surya Prakash Rao, Department of Chemistry, Pondicherry
University, Puducherry–605 014, India. E-mail: hspr.che@pondiuni.edu.in
232

Microwave-Mediated Cycloaddition of Azides
233
The reaction of cholesteryl propargyl ether 1a with benzyl azide 2a to give cycloadduct
3a was selected to evaluate the efficiency of different solvents with 0.1 mol% of copper(II)
sulfate and 0.2 mol% of sodium ascorbate (Scheme 1 and Figure 1). Although neither
cholesteryl propargyl ether 1a and benzyl azide 2a were completely miscible in a 30-fold
excess of 1:1 aqueous methanol, stirring the non-homogenous reaction mixture at rt for 48 h
led to complete reaction in 92% yield as evidenced by the absence of cholesteryl propargyl
ether 1a in TLC; the reaction required only a 5-fold excess of PEG-200 and 2 min for
completion when conducted under microwave (MW) irradiation in a sealed vessel at 110◦C
to provide 99% yield of the cycloadduct 3a. Although the reaction proceeds in better than
90% yield in various solvents such as t-BuOH/H2O (1:1), THF/H2O (1:1), 1,4-dioxane/H2O
(1:1), DMF, ethylene glycol, diethylene glycol, triethylene glycol and tetraethylene glycol,
PEG 200 was selected as the ideal solvent because of the ease of work-up and microwave
absorption capacity. Other polyether solvents investigated, e. g., PEG 400, PEG 4000, mono
methyl ethers of ethylene glycol, diethylene glycol, triethylene glycol or tetraehtylene
glycol and bis-methyl ethers of ethylene glycol, diethylene glycol, triethylene glycol or
tetraehtylene glycol were less effective or gave lower yields. It was determined that the
use of 0.1 mol% of copper(II) sulfate and 0.2 mole% sodium ascorbate was sufficient to
provide the product in less than 3 min. The fact that PEG-200 is practically immiscible
with tert-butyl methyl ether was used in the recovery of the product and to recycle both
the catalyst and the solvent for six runs. After each reaction, 10 mL tert-butyl methyl
ether was added to mixture which was swirled and the solution of the adduct in tert-butyl
methyl ether (upper layer) was separated. This operation was conducted two more times to
recover the product completely. Although the catalytic activity remained excellent for three
runs (97%–99%), on further use of the solvent and the catalyst the yield started to decrease
(85%–94%) with a concurrent increase in the time required to complete the reaction. A study
to determine optimal temperature required in the microwave-mediated reaction revealed
that 110◦C is ideal for high yield and purity of the product. At higher temperatures still,
the yield was lower with considerable charring and at lower temperatures the reaction took
longer time. The microwave-mediated conditions were equally applicable to the reaction
conducted at 4.7 mmol (2 g) scale of 1a to provide nearly quantitative yield of 3a in
5 min.
This MW-mediated CuAAC to provide alcohol-containing natural product triazole
conjugates such as 3a under optimized conditions proved to be general. Treatment of five
propargyl ethers, cholesteryl propargyl ether (1a), menthyl propargyl ether (1b), glucose
diacetonide propargyl ether (1c), thymol propargyl ether (1d) and eugenol propargyl ether
(1e) with benzyl azide 2a, phenyl azide 2b and hexyl azide 2c furnished a library of fifteen
alcohol-triazole conjugates 3a–o (Figure 1). In each case, the products were isolated by
simple dilution of the reaction mixture with excess water. Except for 3a, 3d and 3g the
products are unknown.13,14 The products were characterized by spectroscopic data (1H
NMR, 13C NMR, DEPT), HRMS, combustion analysis and by optical rotation in case of
3a–i. The HRMS and combustion analysis data for unknown samples is given in Table 1.
1
Similarly, H NMR, 13C NMR spectral data and optical rotation data is given in Table 2.
This reaction, however, does not work with acyl and sulfonyl azides since these azides are
not stable under microwave irradiation.

234
Rao and Chakibanda
Figure 1
Structures of Cycloadducts 3a–o. Adduct 3g was reported to be viscous liquid, see Ref. 14.

Microwave-Mediated Cycloaddition of Azides
235
Table 1
Combustion Analysis and HRMS of New Compounds
Combustion Analysis: Calculated (Found)
HRMS (m/z)
Cmpd.
C
H
N
Calculated (Found)
3b
3c
3e
3f
3g
3h
3i
3j
3k
3l
79.51 (79.73)
78.35 (78.36)
72.81 (73.01)
70.98 (70.78)
61.24 (61.41)
60.41 (60.59)
59.27 (59.34)
74.74 (74.95)
74.24 (74.45)
72.34 (72.34)
71.62 (71.65)
71.01 (71.06)
69.27 (69.31)
9.82 (9.84)
11.14 (11.17)
8.68 (8.69)
10.97 (10.98)
6.77 (6.76)
6.52 (6.53)
8.29 (8.27)
7.21 (7.22)
6.89 (6.91)
9.27 (9.27)
6.31 (6.30)
5.96 (5.95)
8.26 (8.24)
7.73 (7.74)
7.61 (7.59)
13.41 (13.43)
13.07 (13.06)
9.74 (9.72)
566.4086 (566.4090)
574.4712 (574.4711)
336.2052 (336.2055)
344.2678 (344.2675)
454.1954 (454.1954)
440.1798 (440.1795)
448.2424 (448.2412)
344.1735 (344.1739)
330.1582 (330.1580)
338.2208 (338.2208)
358.1531 (358.1529)
344.1375 (344.1373)
330.2176 (330.2374)
10.07 (10.10)
9.88 (9.86)
13.07 (13.09)
13.67 (13.71)
13.32 (13.34)
12.53 (12.50)
13.08 (13.09)
12.76 (12.73)
3m
3n
3o
In conclusion, we have shown that the CuAAC Click reaction works well in PEG-200
under MW irradiation at 110◦C to provide alcohol-triazole conjugates close to quantitative
yield. It is possible to reuse solvent and catalyst at least for two additional runs.
Experimental Section
Analytical thin-layer chromatography (TLC) was performed on silica gel coated on glass
plates (0.25 mm, silica gel G, LOBA Chemicals, UV silica gel GF 254). TLC spots were
visualized under UV light and iodine. Column chromatography was carried out using silica
1
gel 100–200 mesh (LOBA Chemicals) using a hexanes-ethyl acetate eluent mixture. H
and 13C NMR spectra were recorded on a Bruker Avance 400 spectrometer in CDCl3:CCl4
(1:1) and chemical shifts values (δ) are relative to the residual solvent peak (δ 7.26 for 1H, δ
77.0 for 13C) where possible or alternatively to TMS (δ 0.00) as internal standard. Coupling
constants (J) are given in Hz and multiplicities are designated as s (singlet), d (doublet), dd
(doublet of doublet), t (triplet), q (quartet), m (multiplet) or broad (br). DEPT-135 NMR
spectra were recorded for all the samples to determine the number of hydrogen atoms present
on each carbon. Samples for melting point determination were recrystallized from hexane
and ethyl acetate (9:1). Melting points were determined using open-ended capillary tubes
on VEEGO VMP-DS instrument and are uncorrected. The propargyl ethers were prepared
according to literature procedure from the corresponding alcohol or phenols.15–17 Phenyl,
benzyl and hexyl azides were obtained by literature procedures.18,19 CuAAC reactions
were carried out in mono-mode CEM Microwave Synthesizer of the model Discover
System generating 2.45 GHz and using 30 mL thick walled glass tubes sealed with a

236
Rao and Chakibanda
Table 2
Optical Rotation, 1H NMR and 13C NMR Spectral Data of Compounds 3a–3o
Cmpd. [α]2D5
1H NMR (δ)
13C NMR (δ)
3a
−16.0◦ 7.40 (s, 1H),7.35–7.32 (m, 3H), 146.3 (C), 140.4 (C), 134.6 (C), 128.9
7.26–7.24 (m, 2H), 5.49 (s,
2H), 5.30–5.29 (m, 1H),
4.62 (s, 2H), 3.31–3.22 (m,
1H), 2.38–2.31 (m, 1H),
2.23–2.14 (m, 1H),
(CH), 128.5 (CH), 127.9 (CH),
121.7 (CH), 121.6 (CH), 78.7
(CH), 61.6 (CH2), 56.6 (CH), 56.0
(CH), 53.9 (CH2), 50.0 (CH), 42.2
(C), 39.6 (CH2), 39.4 (CH2), 38.9
(CH2), 37.0 (CH2), 36.7 (CH2),
36.1 (CH2), 35.6 (CH), 31.8
2.04–1.78 (m, 6H),
1.59–1.31 (m, 8H), 1.25 (s,
3H), 1.19–1.01 (m, 6H),
0.98 (s, 3H), 0.92–0.85 (m,
12H), 0.67 (s, 3H).
(CH2), 31.7 (CH), 29.5 (CH),
28.19 (CH2), 28.15 (CH), 27.9
(CH2), 24.2 (CH3), 23.7 (CH3),
22.7 (CH2), 22.5 (CH3), 20.9
(CH2), 19.3 (CH), 18.7 (CH3).
3b
−18.0◦ 7.95 (s, 1H),7.75–7.72 (m, 2H), 147.7 (C), 140.7 (C), 137.4 (C), 129.8
7.54–7.50 (m, 2H),
(CH), 128.7 (CH), 122.1 (C),
120.6 (CH), 120.3 (CH), 79.1
(CH), 61.8 (CH2), 57.0 (CH), 56.4
(CH), 50.4 (CH), 42.6 (C), 40.0
(CH2), 39.8 (CH2), 39.3 (CH2),
37.4 (CH2), 37.1 (CH2), 36.4
(CH2), 36.0 (CH), 32.19 (CH2),
32.15 (CH), 28.6 (CH2), 28.2
(CH), 24.5 (CH2), 24.1 (CH2),
23.1 (CH3), 22.8 (CH2), 21.3
(CH3), 20.9 (CH2), 19.6 (CH),
19.0 (CH3), 12.1 (CH3).
7.49–7.41 (m, 1H), 5.34 (d,
J = 5.2 Hz, 2H), 4.75 (s,
2H), 4.62 (s, 2H), 3.39–3.31
(m, 1H), 2.46–2.39 (m, 1H),
2.30–2.21(m, 1H),
2.04–1.81 (m, 3H),
1.91–1.79 (m, 2H),
1.62–1.42 (m, 7H),
1.41–1.30 (m, 4H), 1.25 (s,
3H), 1.16–1.09 (m, 6H),
1.01 (s, 3H), 0.92–0.85 (m,
7H), 0.68 (s, 3H).
3c
−16.0◦ 7.46 (s, 1H), 5.32 (d, J =
4.2 Hz, 1H), 4.66 (s, 2H),
4.32 (t, J = 7.2 Hz, 2H),
3.32–3.26 (m, 1H),
145.9 (C), 140.5 (C), 121.7 (CH),
121.6 (CH), 78.7 (CH2),
61.7(CH2), 56.7 (CH), 56.1 (CH),
50.1 (CH2), 42.3 (C), 39.8 (CH2),
39.5 (CH2), 39.0 (CH2), 37.1
(CH2), 36.2 (CH2), 35.7 (CH),
31.9 (CH2), 31.8 (CH), 31.1
(CH2), 30.2 (CH2), 28.3 (CH2),
28.2 (CH), 28.0 (CH), 26.1 (CH2),
24.3 (CH2), 23.8 (CH2), 22.8
(CH3), 22.6 (CH2), 22.4 (CH2),
21.0 (CH2), 19.3 (CH3), 18.7
(CH3), 13.9 (CH2), 11.9 (CH3).
(Continued on next page)
2.41–2.34 (m, 1H),
2.29–2.28 (m, 1H),
2.03–2.78 (m, 7H),
1.68–0.81 (m, 42H), 0.68 (s,
3H).

Microwave-Mediated Cycloaddition of Azides
237
Table 2
Optical Rotation, 1H NMR and 13C NMR Spectral Data of Compounds 3a–3o (Continued)
Cmpd. [α]2D5
3d
1H NMR (δ)
13C NMR (δ)
−83.3◦ 7.39 (s, 1H), 7.34–7.31 (m,
3H), 7.31–7.23 (m, 2H),
5.48 (s, 2H), 4.71 (d, J =
12.0 Hz, 1H), 4.53 (d, J =
12.0 Hz, 1H), 3.13 (td, J =
10.5, 4.0 Hz, 1H), 2.15–2.07
(m, 3H), 1.64–1.56 (m, 3H),
1.39–1.29 (m, 1H),
146.5 (C), 134.7 (C), 128.9 (CH),
128.5 (CH), 127.9 (CH), 121.9
(CH), 78.5 (CH), 61.8 (CH2), 53.9
(CH2), 48.1 (CH), 40.2 (CH2),
34.5 (CH2), 31.4 (CH), 25.4 (CH),
23.3 (CH2), 22.3 (CH3), 20.9
(CH3), 16.1 (CH3).
1.23–1.13 (m, 1H), 0.91 (d,
J = 6.5 Hz, 3H), 0.83 (d, J
= 7.0 Hz, 4H), 0.59 (d,
J = 7.0 Hz, 3H).
3e
−83.8◦ 7.91 (s, 1H), 7.74–7.72 (m,
2H), 7.52–7.48 (m, 2H),
7.43–7.39 (m, 1H), 4.85 (d,
J = 12.4 Hz, 1H), 4.63 (d, J
= 12. Hz, 1H), 3.23 (td, J =
12.0, 4.0 Hz, 1H), 2.24–2.18
(m, 3H), 1.64–1.59 (m, 3H),
1.44–1.34 (m, 1H),
147.0 (C), 137.2 (C), 129.6 (CH),
128.4 (CH), 120.4 (CH), 120.0
(CH), 78.9 (CH), 61.9 (CH2), 48.2
(CH), 40.2 (CH2), 34.5 (CH2), 31.5
(CH), 25.6 (CH), 23.3 (CH2), 22.4
(CH3), 21.0 (CH3), 16.2 (CH3).
1.29–1.21 (m, 1H), 0.94 (d,
J = 8.0 Hz, 3H), 0.88 (d, J
= 7.2 Hz, 4H), 0.70 (d, J =
8.0 Hz, 3H).
3f
−83.5◦ 7.42 (s, 1H), 4.70 (d, J =
12.2 Hz, 1H), 4.52 (d, J =
12.2 Hz, 1H), 4.29 (t, J =
7.2 Hz, 2H), 3.15 (td, J =
10.5, 4.1 Hz, 1H), 2.17–2.11
(m, 3H), 1.87 (t, J = 7.0 Hz,
3H), 1.64–1.26 (m, 3H),
1.33–1.19 (m, 2H), 0.91 (d,
J = 6.5 Hz, 9H), 0.86(d, J =
2.7 Hz, 6H), 0.62 (d, J =
6.9 Hz, 3H).
146.3 (C), 121.8 (CH), 78.7 (CH),
62.1 (CH2), 50.3 (CH2), 48.4 (CH),
40.4 (CH2), 34.7 (CH2), 31.6 (CH),
31.3 (CH2), 30.5 (CH2), 29.3
(CH2), 25.7 (CH2), 23.5 (CH2),
22.6 (CH2), 22.5 (CH3) 21.2
(CH3), 16.4 (CH3), 14.1 (CH3).
3g
−84.5◦ 7.51 (s, 1H), 7.38–7.33 (m,
3H), 7.26–7.23 (m, 2H),
5.80 (d, J = 4.0 Hz, 1H),
5.50 (s, 2H), 4.78 (q, J =
10.7 Hz, 2H), 4.53 (d, J =
3.6 Hz, 1H), 4.25–4.20 (m,
1H), 4.04–4.00 (m, 3H),
3.99–3.91 (m, 1H), 1.46 (s,
3H), 1.34 (s, 3H), 1.28 (s,
3H), 1.25 (s, 3H).
134.6 (C), 129.1 (CH), 128.7 (CH),
127.9 (CH), 111.6 (C), 108.9 (C),
105.1 (C), 82.5 (CH), 81.6 (CH),
81.0 (CH), 72.2 (CH), 67.4 (CH2),
64.0 (CH2), 54.1 (CH2), 26.8 (2 x
CH3), 26.2 (CH3), 25.4 (CH3).

238
Rao and Chakibanda
Table 2
Optical Rotation, 1H NMR and 13C NMR Spectral Data of Compounds 3a–3o
Cmpd.
[α]2D5
1H NMR (δ)
13C NMR (δ)
3h
−84.8◦ 8.10 (s, 1H), 7.72–7.69 (m, 2H),
7.50–7.46 (m, 2H), 7.41–7.39
(m, 1H), 5.81 (d,
145.8 (C), 137.3 (C), 129.8 (CH), 128.7
(CH), 120.5 (CH), 120.4 (CH), 111.9
(C), 109.2 (C), 105.3 (CH), 82.7 (CH),
81.6 (CH), 81.2 (CH), 72.3 (CH), 67.6
(CH2), 64.0 (CH2), 27.1 (CH3), 27.0
(CH3), 26.4 (CH3), 25.7 (CH3).
J = 3.6 Hz, 1H), 4.85 (q, J =
15.9 Hz, 2H), 4.85 (q, J =
3.6 Hz, 1H), 4.33–4.28 (m,
1H), 4.08–4.00 (m, 3H),
3.97–3.94 (m, 1H), 1.44 (s,
3H), 1.36 (s, 3H), 1.31 (s, 3H),
1.27 (s, 3H).
3i
−85.9◦ 7.59 (s, 1H), 5.88 (d, J = 4.0 Hz,
2H), 4.70 (q, J = 12.0 Hz, 2H),
4.53 (d, J = 3.6 Hz, 1H), 4.33
(t, J = 8.0 Hz, 1H), 4.12–4.07
(m, 4H), 4.05–4.00 (m, 3H),
1.90 (s, 2H), 1.67(s, 2H), 1.49
(s, 3H), 1.42 (s, 3H), 1.36 (s,
3H), 1.34 (s, 3H), 1.31–1.29
(m, 3H), 0.88 (t, J = 8.0 Hz,
3H).
144.8 (C), 122.1 (CH), 111.8 (C), 109.0
(C), 105.2 (CH), 82.6 (CH), 81.6
(CH), 81.1 (CH), 72.4 (CH), 67.4
(CH2), 64.4 (CH2), 50.4 (CH2), 31.1
(CH2), 30.2 (CH2), 29.7 (CH2), 26.8
(CH3), 26.8 (CH3), 26.2 (CH3), 26.1
(CH3), 25.5 (CH2), 22.4 (CH2), 13.9
(CH3).
3j
—
7.47 (s, 1H), 7.38–7.33 (m, 3H),
7.25–7.23 (m, 2H), 7.06 (d, J
= 7.5 Hz, 1H), 6.74 (s, 1H),
6.72 (s, 1H), 5.51 (s, 2H), 5.17
(s, 2H), 3.23 (m, 1H), 2.30 (s,
3H), 1.17 (s, 3H), 1.15 (s, 3H).
155.4 (C), 145.3 (C), 136.3 (C), 134.8
(C), 134.2 (C), 129.2 (CH), 128.8
(CH), 128.0 (CH), 126.1 (CH), 122.1
(CH), 122.0 (CH), 113.0 (CH), 62.6
(CH2), 54.2 (CH2), 26.6 (CH), 22.9
(2xCH3), 21.5 (CH3).
3k
—
7.98 (s, 1H), 7.76–7.74 (m, 2H),
7.52 (m, 2H), 7.45–7.40 (m,
1H), 7.07 (d, J = 7.6 Hz, 1H),
6.80 (s, 1H), 6.76 (d, J =
7.7 Hz, 1H), 5.29 (s, 2H), 3.31
(m, 1H), 2.34 (s, 3H), 1.23 (s,
3H), 1.21 (s, 3H).
155.4 (C), 145.8 (C), 137.4 (C), 136.5
(C), 134.3 (C), 129.9 (CH), 128.8
(CH), 126.2 (CH), 122.2 (CH), 120.7
(CH), 120.2 (CH), 112.9 (CH), 62.6
(CH2), 26.8 (CH), 23.1 (2xCH3), 21.6
(CH3).
3l
—
7.53 (s, 1H), 7.05 (d, J = 7.6 Hz,
1H), 6.74 (s, 1H), 6.72 (d, J =
7.7 Hz, 1H), 5.17 (s, 2H), 4.31
(t, J = 7.2 Hz, 2H,), 3.29–3.22
(m, 1H), 2.29 (s, 3H), 1.89 (t, J
= 6.9 Hz, 2H), 1.32–1.29 (m,
6H), 1.27 (s, 3H), 1.26 (s, 3H),
1.18 (t, J = 7.2 Hz, 3H).
155.3 (C), 144.6 (C), 136.1 (C), 134.0
(C), 125.9 (CH), 121.9 (CH), 121.7
(CH), 112.7 (CH), 62.5 (CH2), 50.2
(CH2), 31.1 (CH2), 30.2 (CH2), 26.6
(CH2), 26.1 (CH2), 22.8 (2xCH3),
22.4 (CH3), 21.3 (CH2),13.9 (CH3).
(Continued on next page)

Microwave-Mediated Cycloaddition of Azides
239
Table 2
Optical Rotation, 1H NMR and 13C NMR Spectral Data of Compounds 3a–3o (Continued)
Cmpd.
[α]2D5
1H NMR (δ)
13C NMR (δ)
3m
—
7.50 (s, 1H), 7.68–7.66 (m, 2H),
7.45–7.41 (m, 2H), 7.37–7.33
(m, 1H), 6.89 (d,
148.5 (C), 144.9 (C), 143.6, (C), 136.3
(C), 133.6 (C), 132.5 (C), 127.9 (CH),
127.4 (CH), 126.9 (CH), 121.6 (CH),
119.4 (CH),114.6 (CH), 113.6 (CH),
111.2 (CH), 62.3 (CH2), 54.5 (CH3),
52.8 (CH2), 38.7 (CH2).
J = 8.0 Hz, 1H), 6.64–6.62 (m,
2H), 5.94–5.86 (m, 1H), 5.43
(s, 2H), 5.15 (s, 2H), 5.06–5.01
(m, 2H), 3.75 (s, 3H), 3.29 (d,
J = 8.0 Hz, 2H).
3n
—
8.03 (s, 1H), 7.68–7.66 (m, 2H),
7.45–7.41 (m, 2H), 7.37–7.33
(m, 1H), 6.93 (d,
149.6 (C), 146.0 (C), 145.2 (C), 137.5
(C), 137.1 (C), 133.7 (CH), 129.6
(CH), 128.6 (CH), 120.8 (CH), 120.7
(CH), 120.4 (CH), 115.8 (CH2), 114.5
(CH), 112.4 (CH), 63.3 (CH2), 55.7
(CH3), 39.9 (CH2).
J = 7.9 Hz, 1H), 6.66–6.63 (m,
2H), 5.94–5.86 (m, 1H), 5.85
(s, 2H), 5.26–5.00 (m, 2H),
3.81 (s, 3H), 3.28–3.27 (d, J =
6.6 Hz, 2H).
3o
—
7.56 (s, 1H), 6.91 (d, J = 7.9 Hz,
149.5 (C), 146.0 (C), 144.4 (C), 137.4
(CH), 133.4 (C), 122.2 (CH), 120.6
(CH), 115.7 (CH2), 114.5 (CH), 112.3
(CH), 63.4 (CH2), 55.7 (OCH3), 50.2
(CH2), 39.8 (CH2), 31.1 (CH2), 30.2
(CH2), 26.1 (CH2), 22.4 (CH2), 13.9
(CH3).
1H), 6.67–6.64 (m, 2H),
5.94–5.86 (m, 1H), 5.23 (s,
1H), 5.07–5.02 (m, 2H), 4.31
(t, J = 7.2 Hz, 2H), 3.84 (s,
3H), 3.30 (d, J = 6.6 Hz, 2H),
1.88–1.86 (m, 2H), 1.33–1.25
(m, 6H), 0.89–0.86 (m, 3H).
rubber septum. The contents of the reaction vessel were stirred while the temperature was
maintained at 110◦C. At this temperature internal pressure of the reaction vessel did not
exceed 1 bar (750 mm Hg).
1-Benzyl-4-[(cholesteryloxy)methyl]-1H-1,2,3-triazole (3a). Typical Procedure. A
heterogeneous mixture of cholesterol propargyl ether (1a, 2 g, 4.7 mmol), benzyl azide
.
(2a, 629 mg, 4.7 mmol), CuSO4 5H2O (5.1 mg, 0.001 mmol), sodium ascorbate (9.9 mg,
0.002 mmol) and PEG 200 (4.71 g, 5 equiv) in a 30 ml thick walled glass tube fitted with
a rubber septum was irradiated at 110◦C for 5 min, by which time reaction was complete
(TLC). The reaction mixture was diluted with ice-cold distilled water (20 mL) to afford a
solid suspension which was collected (2.62 g, 99%). Although this sample was sufficiently
pure (TLC) for IR and NMR spectra, for the purposes of mp determination, HRMS and
combustion analysis a part of the sample was recrystallized from a mixture of hexanes and
ethyl acetate (9:1).
Acknowledgments
H. S. P. Rao thanks University Grants Commission (UGC) Special Assistance Program
(SAP) and Fund for Improvement of Science and Technology Infrastructure in Universi-
ties and Higher Educational Institutions (FIST), Department of Science and Technology

240
Rao and Chakibanda
for financial assistance. CG thanks UGC for Meritorious Fellowship. We thank Central
Instrumentation Facility, Pondicherry University, Organic Chemistry Department, Indian
Institute of Science, Bangalore and Indian Institute of Technology, Chennai, for recording
the spectra and providing the analysis data.
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