Direct iodination of monosubstituted aryl acetylenes and acetylenic ketones

Article abstract of DOI:10.1080/00397910701749724

Monosubstituted acetylenes were iodinated to form iodoacetylenes under simple conditions. Reaction of aryl acetylenes with molecular iodine in the presence of 4-dimethylaminopyridine (DMAP) gave the desired products in good to excellent yields. Iodination

Full text of DOI:10.1080/00397910701749724

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Direct Iodination of Monosubstituted Aryl
Acetylenes and Acetylenic Ketones
Ling‐Guo Meng a , Pei‐Jie Cai a , Qing‐Xiang Guo a & Song Xue a
a Department of Chemistry , University of Science and Technology of China ,
Hefei, China
Published online: 18 Jan 2008.
To cite this article: Ling‐Guo Meng , Pei‐Jie Cai , Qing‐Xiang Guo & Song Xue (2008) Direct Iodination of
Monosubstituted Aryl Acetylenes and Acetylenic Ketones, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 38:2, 225-231, DOI: 10.1080/00397910701749724
To link to this article: http://dx.doi.org/10.1080/00397910701749724
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Synthetic Communicationsw, 38: 225–231, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701749724
Direct Iodination of Monosubstituted Aryl
Acetylenes and Acetylenic Ketones
Ling-Guo Meng, Pei-Jie Cai, Qing-Xiang Guo, and Song Xue
Department of Chemistry, University of Science and Technology
of China, Hefei, China
Abstract: Monosubstituted acetylenes were iodinated to form iodoacetylenes under
simple conditions. Reaction of aryl acetylenes with molecular iodine in the presence
of 4-dimethylaminopyridine (DMAP) gave the desired products in good to excellent
yields. Iodination of aryl acetylenic ketones using K2CO3 as base was also described.
Keywords: acetylenic ketones, bases, iodination, terminal alkynes
Iodoacetylenes are useful intermediates in organic synthesis,[1] and medicinal
and pharmaceutical research.[2] Numerous synthetic methods for their prep-
aration have been developed.[3] The usual preparative methods include iodina-
[1c,4]
Na,[5] or Mg[6]) performed
;;
tion of metal aceylides RC CM (M¼Li,
from terminal acetylenes. The direct iodination of terminal alkynes using
ZnI2,[3d] silver nitrate,[1b,3f] morphine,[1a,2a,3g] liquid ammonia,[7] and tetrabu-
tylammonium trifluoroacetate[8] have also been reported. Herein, we describe
an alternative methodology to synthesize iodoacetylenes by direct iodination
of monosubstituted acetylenes using molecular iodine and a base.
Received March 22, 2007
Address correspondence to Song Xue, Department of Chemistry, University of
Science and Technology of China, 96 JinZhai Rd., Hefei 230026, China. E-mail:
xuesong@ustc.edu.cn
225

226
L.-G. Meng et al.
RESULTS AND DISCUSSION
To begin our study, phenylacetylene was chosen as a representative substrate
for reaction conditions. Treatment of phenylacetylene with 1.1 equiv of
4-dimethylaminopyridine (DMAP) and 1.1 equiv of molecular iodine in
CH2Cl2 under reflux for 6 h afforded (2-iodoethynyl)benzene (2a) in 90%
yield. When the reaction was stirred at room temperature, 88% yield of the
desired product was obtained by prolonging reaction time to 24 h. When 1.1
equiv of 1,4-diazabicyclo[2,2,2]octane (DABCO) was used as a base, the
desired product 2a was obtained in a low yield (64%) under the same con-
ditions. However, the choice of pyridine and Et3N as base gave a mixture
of (2-iodoethynyl)benzene (2a) and (1,2-diiodovinyl)benzene in combined
63% and 24% yields, respectively. Thus, DMAP as a base was crucial for
the course of this reaction. The use of toluene and diethyl ether as solvent
led to the formation of the desired product 2a in 32% and 22% yields,
respectively.
Subsequently, various terminal acetylenes were submitted to the reaction,
and the results are shown in Table 1. Aryl acetylenes could be converted to the
corresponding 1-iodo-1-alkynes effectively, and the substrate with an
electron-withdrawing group on the aromatic ring gave better yield than that
of an electron-donating group on the aromatic ring. Treatment of
Table 1. Iodination of terminal acetylenes using DMAP
Entry
Ar
Time (h)
Product
Yielda (%)
1
2
3
4
5
6
7
8
9
C6H5
6
6
2a
2b
2c
2d
2e
2f
90
95
85
93
88
97
96
87
83
p-ClC6H4
o-ClC6H4
p-BrC6H4
o-BrC6H4
p-NO2C6H4
m-NO2C6H4
p-EtC6H4
p-MeOC6H4
10
10
10
10
10
10
12
2g
2h
2i
10
12
92b
aIsolated yields.
bDMAP (2.2 eq.) and iodine (2.2 eq.) were used.

Monosubstituted Aryl Acetylenes and Acetylenic Ketones
227
1,4-diethynylbenzene with 2.2 equiv of DMAP and 2.2 equiv of iodine in
CH2Cl2 under reflux for 12 h afforded the desired product 2j in 92% yield.
The reactions reported in Table 1 were clean, taking place with only trace
amounts of 1,2-diiodoalkenes. The iodination of alkyl acetylene, however,
was very slow under the similar conditions. For example, treatment of
1-octyne with DMAP and molecular iodine in CH2Cl2 at reflux for 12 h
afforded a mixture of 1-iodooct-1-yne and 1,2-diiodooct-1-ene, which were
1
not separated by silica-gel column chromatography. H NMR spectra of the
crude mixture indicated that only 37% of start materials was converted to
1-iodooct-1-yne and 1,2-diiodooct-1-ene with a ratio of 4:1. The iodination
of alkyl acetylenes with diminished efficiency might be ascribed to the
lower reactivity of alkyl acetylenes than that of aryl acetylenes.
Based on this work, we further study the iodination of terminal acetylenic
ketones, which should be more reactive than aryl acetylenes. When 1-phenyl-
prop-2-yn-1-one 3a was submitted to the reaction under the standard con-
ditions, no iodoacetylene was obtained. Fortunately, iodination of acetylenic
ketones proceeded smoothly when inorganic base K2CO3 was used instead
of DMAP. Reaction of substrate 3a with 1.1 equiv of K2CO3 and 1.1
equiv of molecular iodine in CH2Cl2 under reflux for 5 h afforded the
Table 2. Iodination of acetylene ketones with iodine and bases
Entry
R
Base
Product
Yielda (%)
1
2
C6H5
C6H5
C6H5
K2CO3
K2CO3
K2CO3
KHCO3
KOH
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
71b
82
70c
,5
23
13
83
84
80
88
89
55
3
4
C6H5
C6H5
C6H5
5
6
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
7
p-ClC6H4
o-ClC6H4
p-FC6H4
p-MeOC6H4
trans-C6H5CH55CH
OC2H5
8
9
10
11
12
4g
aIsolated yields.
bAt reflux.
cAt 2108C.

228
L.-G. Meng et al.
3-iodo-1-phenylprop-2-yn-1-one 4a in 71% yield (entry 1, Table 1). The yield
of the desired product was improved to 82% at 08C. When other inorganic
bases, such as KHCO3, KOH, and Na2CO3, were used, much lower yields
were obtained. Hence, K2CO3 was used to react with acetylenic ketones and
molecular iodine for 5 h in CH2Cl2 at 08C as the standard conditions. Sub-
sequently, various acetylenic ketones were submitted to the reaction under
the standard conditions, and representative results are shown in Table 2. As
we described previously, aryl acetylenic ketones could be converted to the
corresponding products. The substituents on the aromatic ring have no
obvious effect on the reaction. The substrate containing electron-poor olefin
underwent a selective iodination reaction in preference to addition of the
olefin under our standard reaction conditions (entry 11, Table 2). Ethyl propio-
late was also converted to the desired product, albeit the yield was moderate
(entry 12, Table 2). However, 3-butyn-2-one as substrate gave an unidentified
complex mixture. To date, there have been no reports of the iodination of acet-
ylenic ketones. Therefore, a simple and efficient procedure involving mild
conditions was provided to iodinate the aromatic acetylenic ketones.
In summary, we have developed an efficient method for the preparation of
iodoacetylenes. The iodination reaction of aryl acetylenes with molecular iodine
proceeded smoothly in the presence of DMAP, giving the desired products in
good to excellent yields. The aryl acetylenic ketones were iodinated by
molecular iodine and K2CO3 in good yields under mild conditions.
EXPERIMENTAL
Infrared (IR) spectra were run on a Bruker AC spectrometer and expressed
in centimeters21. NMR spectra were recorded on a Bruker AVMCE-
300 MHz in CD3Cl solutions. High-resolution mass spectra were obtained
with a Micromass GCT TOF mass spectrometer.
General Procedure for the Direct Iodination of Monosubstituted
Aryl Acetylenes (Representative Procedure for Compound 2a)
Phenylacetylene (0.5 mmol) was added to a solution of DMAP (0.55 mmol)
and iodine (0.55 mmol) in dry CH2Cl2 (2 mL) in a round flask. The
resulting mixture was refluxed for the required length of time. The contents
were cooled at room temperature, washed with sodium thiosulfate to
remove unreacted iodine, and extracted with diethyl ether (3 ꢀ 10 mL). Sub-
sequently, the extract was washed with brine (10 mL), dried over MgSO4, and
concentrated. The crude product was purified by silica-gel chromatography,
and the corresponding product was isolated (102.6 mg, 90% yield).

Monosubstituted Aryl Acetylenes and Acetylenic Ketones
229
General Procedure for the Direct Iodination of Monosubstituted
Acetylenic Ketones (Representative Procedure for Compound 4a)
1-Phenylprop-2-yn-1-one (0.5 mmol) was added at 08C to a solution of K2CO3
(0.55 mmol) and iodine (0.55 mmol) in dry CH2Cl2 (2 mL) in a round flask.
The resulting mixture was stirred for 5 h. The contents were washed with
sodium thiosulfate to remove unreacted iodine and extracted with diethyl
ether (3 ꢀ 10 mL). Then, the extract was washed with brine (10 mL), dried
over MgSO4, and concentrated. The crude product was purified by silica-gel
chromatography, and the corresponding product was isolated (105 mg,
82% yield).
Data for New Compounds
3-Iodo-1-phenylprop-2-yn-1-one (4a): 1H NMR (300 MHz, CDCl3) d, ppm,
8.15 (d, J ¼ 7.6 Hz, 2H), 7.65 (t, J ¼ 7.3 Hz, 1H), 7.52 (m, 2H); 13C NMR
(75 MHz, CDCl3) d, ppm, 176.5, 136.3, 134.6, 129.9, 128.8, 94.1, 20.0; IR
(KBr) v, cm21, 2148, 1613; HRMS (EI) calcd. for C9H5OI (Mþ): 255.9385;
found: 255.9380.
1-(4-Chlorophenyl)-3-iodoprop-2-yn-1-one (4b): 1H NMR (300 MHz,
CDCl3) d, ppm, 8.07 (d, J ¼ 8.5 Hz, 2H), 7.48, (d, J ¼ 8.5 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d, ppm, 175.2, 141.3, 134.7, 131.2, 129.2, 93.8,
21.0; IR (KBr) v, cm21, 2150, 1630; HRMS (EI) calcd. for C9H4OClI
(Mþ): 289.8995; found: 289.9001.
1-(2-Chlorophenyl)-3-iodoprop-2-yn-1-one (4c): 1H NMR (300 MHz,
CDCl3) d, ppm, 8.07 (d, J ¼ 8.1 Hz, 1H), 7.48 (m, 2H), 7.41 (m, 1H); 13C
NMR (75 MHz, CDCl3) d, ppm, 175.0, 134.9, 133.9, 133.8, 133.2, 131.8,
126.9, 95.0, 21.8; IR (KBr) v, cm21, 2145, 1633; HRMS (EI) calcd. for
C9H4OClI (Mþ): 289.8995; found: 289.8992.
1-(4-Fluorophenyl)-3-iodoprop-2-yn-1-one (4d): 1H NMR (300 MHz,
CDCl3) d, ppm, 8.18 (m, 2H), 7.19 (m, 2H); 13C NMR (75 MHz, CDCl3) d,
ppm, 174.9, 166.8, 132.8, 132.7, 116.1, 93.9, 20.3; IR (KBr) v, cm21, 2149,
1629; HRMS (EI) calcd. for C9H4OFI (Mþ): 273.9291; found: 273.9294.
3-Iodo-1-(4-methoxyphenyl)prop-2-yn-1-one (4e): 1H NMR (300 MHz,
CDCl3) d, ppm, 8.11 (d, J ¼ 8.7 Hz, 2H), 6.97 (d, J ¼ 8.7 Hz, 2H), 3.89
(s, 3H); 13C NMR (75 MHz, CDCl3) d, ppm, 175.1, 164.8, 132.3, 129.6,
114.1, 94.1, 55.7, 19.1; IR (KBr) v, cm21, 2150, 1623; HRMS (EI) calcd.
for C10H7O2I (Mþ): 285.9491; found: 285.9488.
(E)-5-Iodo-1-phenylpent-1-en-4-yn-3-one (4f): 1H NMR (300 MHz,
CDCl3) d, ppm, 7.84 (d, J ¼ 16.2 Hz, 1H), 7.65 (m, 2H), 7.43 (m, 3H), 6.79

230
L.-G. Meng et al.
(d, J ¼ 16.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) d, ppm, 176.6, 149.5,
133.9, 131.5, 129.1, 128.8, 127.9, 93.7, 18.7. IR (KBr) v, cm21, 2147,
1644; HRMS (EI) calcd. for C11H7OI (Mþ) 281.9542; found: 281.9538.
ACKNOWLEDGMENTS
We express our appreciation to the National Natural Science Foundation of
China (20776114) and Program of NCET (060551).
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