Reusable and efficient CuI/TBAB-catalyzed iodination of terminal alkynes in water under air

Article abstract of DOI:10.1002/jccs.200900156

An environmentally-friendly and operationally-simple process for the synthesis of 1-iodoalk-1-ynes under mild conditions catalyzed by CuI/TBAB in water under air was developed in this study. Catalyst loadings of CuI as low as 1-2 mol% gave 1-iodoalk-1-yne

Full text of DOI:10.1002/jccs.200900156

1078
Journal of the Chinese Chemical Society, 2009, 56, 1078-1081
Note
Reusable and Efficient CuI/TBAB-catalyzed Iodination of Terminal Alkynes
in Water under Air
Shao-Nung Chen (
Tze-Chiao Lin (
), Tzu-Ting Hung (
) and Fu-Yu Tsai* (
),
)
Institute of Organic and Polymeric Materials, National Taipei University of Technology,
1, Sec. 3, Chung-Hsiao E. Rd., Taipei 106, Taiwan, R.O.C.
An environmentally-friendly and operationally-simple process for the synthesis of 1-iodoalk-1-ynes
under mild conditions catalyzed by CuI/TBAB in water under air was developed in this study. Catalyst
loadings of CuI as low as 1-2 mol% gave 1-iodoalk-1-ynes in good to high yields, and the residual aqueous
solution after extraction with hexane could be reused for the next reaction without any treatment.
Keywords: Reusable catalyst; Green chemistry; Copper(I) iodide; 1-Iodoalk-1-yne; Water.
INTRODUCTION
1-Iodoalk-1-ynes are useful intermediates in organic
organic products and reusable.16-22 We have reported the
homocoupling of terminal alkynes catalyzed by a cationic
2,2¢-bipyridyl palladium/CuI system in water using I2 as an
oxidant, resulting in 1-iodoalk-1-yne being formed in a
20% yield when the co-catalyst, CuI, was fixed at 1 mol%
and the palladium catalyst was reduced to 0.0001 mol%.23
This result prompted us to develop a reusable and efficient
CuI/TBAB (tetrabutylammonium bromide) system-cata-
lyzed process for the iodination of terminal alkynes under
mild conditions in water under air (Scheme I).
synthesis1-5 and pharmaceutical research.6,7 Most prepara-
tive methods involve iodination of stoicheiometric amounts
of metal acetylides to generate 1-iodoalk-1-ynes (M = Li,8,9
Na,10 Mg11); however, these methods use and generate
moisture-sensitive organometallic reagents and intermedi-
ates, requiring the reactions to be performed under an inert
atmosphere and reducing the tolerance of polar functional
groups on the alkynes. There have been reports of the io-
dination of 1-alkynes avoiding the use of moisture-sensi-
tive organometallic reagents; for instance, 1-iodoalk-1-
ynes can be prepared by the reaction of terminal alkynes
with polymer-supported electrophilic reagents,12 and aryl
acetylenes can be iodinated by I2 in the presence of 4-di-
methylaminopyridine in CH2Cl2 under reflux conditions.13
On the other hand, transition-metal catalysts, especially
CuI, are of great interest for the iodination of terminal al-
kynes, as they can reduce the use of metal, enabling the tol-
eration of a wide range of functional groups on the alkynes.
Usually, this terminal alkyne iodination reaction is con-
ducted in DMF or MeCN under mild conditions in the pres-
ence of I2 or a hypervalent iodine reagent using 5-10 mol%
of CuI as the catalyst.14,15
CuI/TBAB-catalyzed iodination of ter-
minal alkynes
Scheme I
CuI (1-2 mol%), TBAB (1 eq)
R
+ I2
R
I
Et3N (3 eq), H2O, rt, 24h
1
2
RESULTS AND DISCUSSION
To optimize the reaction conditions, 1-octyne (1a)
was chosen as the representative reactant. As shown in Ta-
ble 1, when we used the terminal alkyne homocoupling
conditions that we reported previously, using only CuI as
catalyst, this resulted in a 47% yield of 1-iodooct-1-yne
(2a) (Entry 1). However, only 30% of 2a was obtained
when the quantity of TBAB was doubled (Entry 2). Under
these conditions, the homocoupling by-product was not ob-
The use of water as a solvent in organic reactions has
garnered much attention recently: not only is it cheap, envi-
ronmentally benign, and inflammable, but it also has the
feature that the catalyst in water may be separable from the
* Corresponding author. Fax: +886-2-2731-7174; E-mail: fuyutsai@ntut.edu.tw (F.-Y. Tsai)

Synthesis of 1-Iodoalk-1-ynes in Water
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1079
bearing polar functional groups were also studied; the io-
dinated products were isolated in moderate to good yields
in the presence of 1 mol% CuI (Entries 4-6 and 8). With
higher catalyst loading (2 mol%), the iodination yields of
1g and 1h could be improved effectively (Entries 7 and 9).
As for aryl acetylenes, phenylacetylene and ethynyltol-
uenes, 1i-1k were studied, and under identical conditions
the corresponding 1-iodoar-1-ynes, 2i-2k, were isolated in
42-68% yields (Entries 10-12). As a slower reaction rate
was observed for 1k, a catalyst loading of 2 mol% was ap-
plied in this case in order to obtain a higher yield (Entry
13). However, phenylacetylenes with electron-withdraw-
ing groups, such as acetyl and cyanide groups at the para
position of aromatic rings, were ineffective for iodination,
even when a higher catalyst loading (10 mol%) was em-
ployed (Entries 14 and 15). These negative results were
presumably due to the solid phenylacetylene derivatives
being unable to be brought into the aqueous phase by
TBAB.
Table 1. Iodination of 1-octyne (1a) catalyzed by CuI/TBAB in
watera
Entry
Base I2 (equiv) TBAB (equiv) Product Yield (%)b
1
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
KOH
K2CO3
1
1
2
2
2
2
3
2
2
0.5
1
2a
2a
2a
2a
2a
2a
2a
2a
2a
47
30
45
95
92
62
82
2
2
3
0.5
1
4
5c
6d
7
1
1
1
8
1
9
1
0e
a Reaction conditions: 1-octyne (1 equiv), CuI (1 mol%), base (3
equiv), I2, and TBAB at room temperature for 24 h.
b Isolated yields.
c Recycled catalyst was used.
d Second run employed recycled catalyst.
e A 47% yield of the homocoupling product was found.
served. The employment of phase transfer agent TBAB to
bring the organic reactant, 1-octyne, across the interface
into the aqueous phase is essential to facilitate iodination in
water. It was found that doubling the amounts of both I2 and
TBAB afforded the best results in the presence of 1 mol%
of CuI (Entries 3 and 4). After extraction of the reaction
mixture of Entry 4 with hexane (5 mL) three times, the re-
sidual aqueous solution was able to catalyze the further io-
dination of 1-octyne, giving a 92% yield for the first and a
62% yield for the second reuse runs (Entries 5 and 6, re-
spectively). It is noteworthy that although the activity of
the catalyst in the second reuse run (Entry 6) decreased, to
the best of our knowledge, there have been no previous re-
ports of a reusable copper catalyst for the iodination of ter-
minal alkynes. Our system not only uses a green solvent as
the reaction medium, but also facilitates the separation of
the catalyst from the organic products and enables its reuse
via an operationally-simple procedure. Further increasing
the amount of I2 resulted in a slightly lower yield than pro-
duced in Entry 4 (Entry 7), whereas inorganic bases such as
KOH and K2CO3 were ineffective for this iodination reac-
tion (Entries 8 and 9).
CONCLUSION
We have successfully employed an environmentally-
friendly and operationally-simple CuI/TBAB catalytic sys-
tem for the iodination of terminal alkynes in water under
air. This efficient and green procedure using water as a sol-
vent enables the reuse of the catalyst and is tolerant towards
polar functional groups on the alkynes, making this cata-
lytic system green and synthetically useful.
EXPERIMENTAL SECTION
General
All chemicals were purchased from commercial sup-
pliers and were used without further purification. All 1H
and 13C NMR spectra were recorded in CDCl3 at 25 °C on a
Varian 200 NMR spectrometer. All known products and
their spectra were in agreement with authentic samples.
General procedure for the iodination of terminal al-
kynes
A 20-mL reactor was charged with CuI (1 or 2 mol%,
see Table 2), TBAB (1 mmol), and H2O (3 mL). The mix-
ture was stirred at room temperature for 5 min, and Et3N (3
mmol) and I2 (2 mmol) were then added. After stirring of
the mixture for an additional 5 min, the terminal alkyne was
added and the resulting mixture was stirred at room temper-
ature for 24 h. The mixture was then extracted with hexane
or EtOAc and the organic phase was washed with saturated
Na2S2O3. The organic layer was dried over MgSO4 and the
With the optimized reaction conditions in hand, a va-
riety of terminal alkynes were used to explore the scope of
this green catalytic system, and the results are shown in Ta-
ble 2. Alkyl, cycloalkyl and cycloalkenyl terminal alkynes
were iodinated at room temperature in water under air suc-
cessfully, providing the corresponding 1-iodoalk-1-ynes,
2b-2d, in 76-87% yields (Entries 1-3). Terminal alkynes

1080 J. Chin. Chem. Soc., Vol. 56, No. 5, 2009
Chen et al.
Table 2. Iodination of 1-alkynes catalyzed by CuI/TBAB in watera
Entry
1
Alkyne
CH3(CH2)7
CuI (mol%)
1
1-Iodoalkyne
CH3(CH2)7
Yield (%)b
87
I
1b
1c
2b
2c
2
1
76
I
I
3
4
1d
1e
1
1
2d
2e
82
82
HOCH2CH2
HOCH2CH2
HO
I
5
6
1f
1
1
2f
84
45
I
HO
HO
HO
1g
2g
I
7
8
9
1g
1h
1h
2
1
2
2g
2h
2h
71
41
77
I
AcO
AcO
10
1i
1
2i
68
I
I
11
1j
1
2j
67
12
13
14
1k
1k
1l
1
2
2k
2k
2l
42
75
0
I
10
NC
O
NC
I
O
15
1m
10
2m
0
I
a Reaction conditions: alkyne (1 equiv), CuI (1-2 mol%), TBAB (1 equiv), Et3N (3 equiv), I2
(2 equiv), and H2O (3 mL) at room temperature for 24 h.
b Isolated yields.
solvent was removed in a vacuum. After passing through a
29.0, 28.8, 28.5, 22.7, 20.8, 14.1, -7.4.
short silica gel column eluted with hexane or EtOAc, the
solvent was removed by a rotary evaporator and the desired
product was obtained by reduced-pressure distillation.
1-Iodooct-1-yne (2a)24
1H NMR (CDCl3, 200 MHz) d 2.36 (t, J = 6.4 Hz,
2H), 1.44-1.55 (m, 2H), 1.26-1.40 (m, 6H), 0.89 (t, J = 6.4
Hz, 3H); 13C NMR (CDCl3, 50 MHz) d 94.8, 31.3, 29.7,
28.5, 22.5, 20.8, 14.0, -7.6.
Iodoethynylcyclohexane (2c)
1H NMR (CDCl3, 200 MHz) d 2.40-2.51 (m, 1H),
1.57-1.74 (m, 4H), 1.18-1.50 (m, 6H); 13C NMR (CDCl3,
50 MHz) d 99.0, 32.5 (2C), 31.2, 25.7, 24.7 (2C), -7.3.
HRMS calcd for C8H11I, 233.9905; found, 233.9903.
1-Iodoethynylcyclohexene (2d)25
1H NMR (CDCl3, 200 MHz) d 6.10 (t, J = 2.0 Hz,
1H), 2.05-2.10 (m, 4H), 1.53-1.62 (m, 4H); 13C NMR
(CDCl3, 50 MHz) d 137.0, 121.2, 96.1, 28.9, 25.5, 22.1,
21.3, 2.2.
1-Iododec-1-yne (2b)4
1H NMR (CDCl3, 200 MHz) d 2.33 (t, J = 6.8 Hz,
2H), 1.42-1.52 (m, 2H), 1.25-1.40 (m, 10H), 0.86 (t, J = 6.8
Hz, 3H); 13C NMR (CDCl3, 50 MHz) d 94.8, 31.8, 29.1,
4-Iodobut-3-yn-1-ol (2e)26
1H NMR (CDCl3, 200 MHz) d 3.66 (t, J = 6.6 Hz,

Synthesis of 1-Iodoalk-1-ynes in Water
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1081
2H), 2.57 (t, J = 6.4 Hz, 2H), 2.21 (br, 1H); 13C NMR
(CDCl3, 50 MHz) d 91.1, 60.7, 24.9, -3.8.
tional Science Council of Taiwan (NSC 96-2113-M-027-
003-MY2).
4-Iodo-2-methylbut-3-yn-2-ol (2f)9
1H NMR (CDCl3, 200 MHz) d 2.37 (br, 1H), 1.49 (s,
6H); 13C NMR (CDCl3, 50 MHz) d 99.0, 66.8, 31.3 (2C),
-0.5.
Received May 19, 2009.
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Experimental procedure for the reuse of the catalytic
aqueous solution
The reaction was conducted following the procedure
described above and 1-octyne was used as the representa-
tive reactant. After the reaction, the aqueous reaction mix-
ture was extracted with hexane (5 mL) under vigorous stir-
ring three times, and the organic product isolated according
to the previously-described procedure. The residual aque-
ous solution was then charged with Et3N, I2, and 1-octyne
for the next reaction.
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ACKNOWLEDGMENTS
The research was financially supported by the Na-